Substituted quinolin-2 (1H) -ones useful as HIV reverse transcriptase inhibitors

ABSTRACT

This invention relates generally to quinolin-2(1H)-ones and derivatives thereof of Formula (I):                    
     or stereoisomeric forms, stereoisomeric mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, pharmaceutical compositions and diagnostic kits comprising the same, methods of using the same for treating viral infection or as assay standards or reagents, and intermediates and processes for making the same.

This application is a Division of application Ser. No. 09/342,083, filed Jun. 29, 1999, U.S. Pat. No. 6,090,821 which claims priority to Provisional Application No. 60/091,203, filed Jun. 30, 1998.

FIELD OF THE INVENTION

This invention relates generally to quinolin-2(1H)-ones which are useful as inhibitors of HIV reverse transcriptase, pharmaceutical compositions and diagnostic kits comprising the same, methods of using the same for treating viral infection or as assay standards or reagents, and intermediates and processes for making the same.

BACKGROUND OF THE INVENTION

Two distinct retroviruses, human immunodeficiency virus (HIV) type-1 (HIV-1) or type-2 (HIV-2), have been etiologically linked to the immunosuppressive disease, acquired immunodeficiency syndrome (AIDS). HIV seropositive individuals are initially a symptomatic but typically develop AIDS related complex (ARC) followed by AIDS. Affected individuals exhibit severe immunosuppression which predisposes them to debilitating and ultimately fatal opportunistic infections.

The disease AIDS is the end result of an HIV-1 or HIV-2 virus following its own complex life cycle. The virion life cycle begins with the virion attaching itself to the host human T-4 lymphocyte immune cell through the bonding of a glycoprotein on the surface of the virion's protective coat with the CD4 glycoprotein on the lymphocyte cell. Once attached, the virion sheds its glycoprotein coat, penetrates into the membrane of the host cell, and uncoats its RNA. The virion enzyme, reverse transcriptase, directs the process of transcribing the RNA into single-stranded DNA. The viral RNA is degraded and a second DNA strand is created. The now double-stranded DNA is integrated into the human cell's genes and those genes are used for virus reproduction.

At this point, RNA polymerase transcribes the integrated DNA into viral RNA. The viral RNA is translated into the precursor gag-pol fusion polyprotein. The polyprotein is then cleaved by the HIV protease enzyme to yield the mature viral proteins. Thus, HIV protease is responsible for regulating a cascade of cleavage events that lead to the virus particle's maturing into a virus that is capable of full infectivity.

The typical human immune system response, killing the invading virion, is taxed because the virus infects and kills the immune system's T cells. In addition, viral reverse transcriptase, the enzyme used in making a new virion particle, is not very specific, and causes transcription mistakes that result in continually changed glycoproteins on the surface of the viral protective coat. This lack of specificity decreases the immune system's effectiveness because antibodies specifically produced against one glycoprotein may be useless against another, hence reducing the number of antibodies available to fight the virus. The virus continues to reproduce while the immune response system continues to weaken. Eventually, the HIV largely holds free reign over the body's immune system, allowing opportunistic infections to set in and without the administration of antiviral agents, immunomodulators, or both, death may result.

There are at least three critical points in the virus's life cycle which have been identified as possible targets for antiviral drugs: (1) the initial attachment of the virion to the T-4 lymphocyte or macrophage site, (2) the transcription of viral RNA to viral DNA (reverse transcriptase, RT), and (3) the processing of gag-pol protein by HIV protease.

Inhibition of the virus at the second critical point, the viral RNA to viral DNA transcription process, has provided a number of the current therapies used in treading AIDS. This transcription must occur for the virion to reproduce because the virion's genes are encoded in RNA and the host cell reads only DNA. By introducing drugs that block the reverse transcriptase from completing the formation of viral DNA, HIV-1 replication can be stopped.

A number of compounds that interfere with viral replication have been developed to treat AIDS. For example, nucleotide analogs, such as 3′-azido-3′-deoxythymidine (AZT), 2′,3′-dideoxycytidine (ddC), 2′,3′-dideoxythymidinene (d4T), 2′,3′-dideoxyinosine (ddI), and 2′,3′-dideoxy-3′-thia-cytidine (3TC) have been shown to be relatively effective in halting HIV replication at the reverse transcriptase (RT) stage.

An active area of research is in the discovery of non-nucleotide HIV reverse transcriptase inhibitors. As an example, it has been found that certain benzoxazinones and quinazolinones are active in the inhibition of HIV reverse transcriptase, the prevention or treatment of infection by HIV and the treatment of AIDS.

U.S. Pat. No. 5,519,021 describes reverse transcriptase inhibitors which are benzoxazinones of the formula:

wherein X is a halogen, Z may be O.

WO 95/29920 describes suksdorfin analogs according to the Formula (III)

which are useful as antiviral and immunostimulating agents. Compounds of this sort are not considered to be part of the present invention.

U.S. Pat. No. 5,358,949 describes carbostyril derivatives of formula (AA)

which are useful as anti-arrhythmia agents. The application describes 3-substituted quinalinones and dihydroquinalinones, generally, wherein n is 0, 1, or 2; R² or R³ can be a variety of groups, however, R² and R³ can not be substituted on the same position at the same time. However, U.S. Pat. No. 5,358,949 does not disclose, by exemplification, compounds wherein R² or R³ are —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, nor compounds wherein n=2 and the 4 position of the quinoline core is disubstituted, nor where R² or R³ are alkenyls. Compounds of U.S. Pat. No. 5,358,949 are not considered to be part of the present invention.

Even with the current success of reverse transcriptase inhibitors, it has been found that HIV patients can become resistant to a single inhibitor. Thus, it is desirable to develop additional inhibitors to further combat HIV infection.

SUMMARY OF THE INVENTION

Accordingly, one object of the present invention is to provide novel reverse transcriptase inhibitors.

It is another object of the present invention to provide a novel method for treating HIV infection which comprises administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt form thereof.

It is another object of the present invention to provide a novel method for treating HIV infection which comprises administering to a host in need thereof a therapeutically effective combination of (a) one of the compounds of the present invention and (b) one or more compounds selected form the group consisting of HIV reverse transcriptase inhibitors and HIV protease inhibitors.

It is another object of the present invention to provide pharmaceutical compositions with reverse transcriptase inhibiting activity comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt form thereof.

It is another object of the present invention to provide a method of inhibiting HIV present in a body fluid sample which comprises treating the body fluid sample with an effective amount of a compound of the present invention.

It is another object of the present invention to provide a kit or container containing at least one of the compounds of the present invention in an amount effective for use as a standard or reagent in a test or assay for determining the ability of a potential pharmaceutical to inhibit HIV reverse transcriptase, HIV growth, or both.

These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors' discovery that compounds of Formula (I):

wherein R¹, R², Q¹, Q², A, W, X, Y, and Z are defined below, stereoisomeric forms, mixtures of stereoisomeric forms, or pharmaceutically acceptable salt forms thereof, are effective reverse transcriptase inhibitors.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[1] Thus, in a first embodiment, the present invention provides a novel compound of Formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:

A is O or S;

W is N or CR³;

X is N or CR^(3a);

Y is N or CR^(3b);

Z is N or CR^(3c);

provided that the number of W, X, Y, and Z which are N, is zero, one or two;

R¹ is cyclopropyl or C₁₋₃ alkyl substituted with 0-7 halogen;

R² is selected from

C₁₋₆ alkyl substituted with 0-2 R⁴,

C₂₋₅ alkenyl substituted with 0-2 R⁴,

C₂₋₅ alkynyl substituted with 0-1 R⁴,

C₃₋₆ cycloalkyl substituted with 0-2 R⁵,

phenyl substituted with 0-2 R⁵, and

3-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R³ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3a) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

alternatively, R³ and R^(3a), when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form —O—CH₂—O—, —O—CH₂—CH₂—O—, or —CH═CH—CH═CH—;

R^(3b) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

alternatively, R^(3a) and R^(3b), when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form —O—CH₂—O—, —O—CH₂—CH₂—O—, or —CH═CH—CH═CH—;

R^(3c) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

alternatively, R^(3b) and R^(3c), when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form —O—CH₂—O—, —O—CH₂—CH₂—O—, or —CH═CH—CH═CH—;

R⁴ is selected from

C₁₋₆ alkyl substituted with 0-2 R⁵,

C₃₋₁₀ carbocycle substituted with 0-2 R⁵,

phenyl substituted with 0-5 R⁵, and a

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R⁵, at each occurrence, is independently selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

Q¹ and Q² are independently selected from

H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷,

C₁₋₃ alkyl substituted by 3-7 halogens;

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁸, and

C₂₋₆ alkynyl substituted with 0-2 R⁸,

alternatively, Q¹ and Q² can be taken together to form ═O;

alternatively, Q¹ and Q² can be taken together to form:

a 3-6 membered spirocyclic ring, said spirocyclic ring containing 0, 1, or 2 oxygen atoms;

R⁷ is selected from

H,

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁹,

C₂₋₆ alkynyl substituted with 0-1 R⁹,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹, and

C₁₋₃ alkyl substituted by 3-7 halogens;

R⁸ is selected from

C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹,

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; and,

R⁹ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, —SO₂NR¹⁴R¹⁵ and C₁₋₃ alkyl substituted by 3-7 halogens;

R¹⁴ and R¹⁵ are independently selected from H and C₁₋₄ alkyl;

alternatively, R¹⁴ and R¹⁵, together with the nitrogen to which they are attached, combine to form a 5-6 membered ring containing 0-1 Oxygen atoms;

R¹⁶ is selected from H, OH, C₁₋₄ alkyl, C₁₋₄ alkoxy, and NR¹⁴R¹⁵;

R¹⁷ is selected from C₁₋₃ alkyl and C₁₋₃ alkoxy; and

R¹⁸ is selected from C₁₋₄ alkyl and phenyl.

[2] In a preferred embodiment, the present invention provides a novel compound of Formula (II),

wherein:

A is O or S;

R¹ is cyclopropyl or C₁₋₃ alkyl substituted with 0-7 halogen;

R² is selected from

C₁₋₆ alkyl substituted with 0-2 R⁴,

C₂₋₅ alkenyl substituted with 0-2 R⁴,

C₂₋₅ alkynyl substituted with 0-1 R⁴,

C₃₋₆ cycloalkyl substituted with 0-2 R⁵,

phenyl substituted with 0-2 R⁵, and

3-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R³ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3a) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3b) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3c) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R⁴ is selected from

C₁₋₆ alkyl substituted with 0-2 R⁵,

C₃₋₁₀ carbocycle substituted with 0-2 R⁵,

phenyl substituted with 0-5 R⁵, and a

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R⁵, at each occurrence, is independently selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

Q¹ and Q² are independently selected from

H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷,

C₁₋₃ alkyl substituted by 3-7 halogens;

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁸, and

C₂₋₆ alkynyl substituted with 0-2 R⁸,

alternatively, Q¹ and Q² can be taken together to form ═O;

alternatively, Q¹ and Q² can be taken together to form:

a 3-6 membered spirocyclic ring, said spirocyclic ring containing 0, 1, or 2 oxygen atoms;

R⁷ is selected from

H,

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁹,

C₂₋₆ alkynyl substituted with 0-1 R⁹,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹, and

C₁₋₃ alkyl substituted by 3-7 halogens;

R⁸ is selected from

C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹,

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; and,

R⁹ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, —SO₂NR¹⁴R¹⁵, and C₁₋₃ alkyl substituted by 3-7 halogens;

R¹⁴ and R¹⁵ are independently selected from H, methyl, ethyl, propyl, and butyl;

R¹⁶ is selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, and NR¹⁴R¹⁵;

R¹⁷ is selected from methyl, ethyl, propyl, methoxy, ethoxy, and propoxy; and

R¹⁸ is selected from methyl, ethyl, propyl, butyl, and phenyl.

[3] In a more preferred embodiment, the present invention provides a novel compound of Formula (II), wherein:

A is O;

R¹ is —CF₃, —CF₂CF₃, or —CF₂CF₂CF₃;

R² is selected from

C₁₋₆ alkyl substituted with 0-2 R⁴,

C₂₋₅ alkenyl substituted with 0-2 R⁴,

C₂₋₅ alkynyl substituted with 0-1 R⁴,

C₃₋₆ cycloalkyl substituted with 0-2 R⁵,

phenyl substituted with 0-2 R⁵, and

3-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R³ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3a) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3b) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3c) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R⁴ is selected from

C₁₋₆ alkyl substituted with 0-2 R⁵,

C₃₋₁₀ carbocycle substituted with 0-2 R⁵,

phenyl substituted with 0-5 R⁵, and a

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R⁵, at each occurrence, is independently selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

Q¹ and Q² are independently selected from

H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷,

C₁₋₃ alkyl substituted by 3-7 halogens;

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁸, and

C₂₋₆ alkynyl substituted with 0-2 R⁸,

alternatively, Q¹ and Q² can be taken together to form ═O;

alternatively, Q¹ and Q² can be taken together to form:

a 3-6 membered spirocyclic ring, said spirocyclic ring containing 0, 1, or 2 oxygen atoms;

R⁷ is selected from

H,

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁹,

C₂₋₆ alkynyl substituted with 0-1 R⁹,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹, and

C₁₋₃ alkyl substituted by 3-7 halogens;

R⁸ is selected from

C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹,

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; and,

R⁹ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, —SO₂NR¹⁴R¹⁵, and C₁₋₃ alkyl substituted by 3-7 halogens;

R¹⁴ and R¹⁵ are independently selected from H, methyl, and ethyl;

R¹⁶ is selected from H, OH, methyl, ethyl, methoxy, ethoxy, and NR¹⁴R¹⁵;

R¹⁷ is selected from methyl, ethyl, methoxy, and ethoxy; and

R¹⁸ is selected from methyl, ethyl, and phenyl.

[4] In an even more preferred embodiment, the present invention provides a novel compound of Formula (II), wherein:

A is O;

R¹ is —CF₃ or —CF₂CF₃;

R² is selected from

C₁₋₃ alkyl substituted with 0-1 R⁴,

C₂₋₃ alkenyl substituted with 0-1 R⁴, and

C₂₋₃ alkynyl substituted with 0-1 R⁴,

R³ is selected from H, methyl, ethyl, —OH, methoxy, ethoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵;

R^(3a) is selected from H, methyl, ethyl, —OH, methoxy, ethoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵;

R^(3b) is H or F;

R^(3c) is selected from H, methyl, —OH, methoxy, and —OCF₃;

R⁴ is selected from

cyclopropyl substituted with 0-1 R⁵,

phenyl substituted with 0-3 R⁵, and a

5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-1 R⁵, wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, 2-imidazolyl, 1-pyrazolyl, 3-pyrazolyl, and 4-pyrazolyl;

R⁵, at each occurrence, is independently selected from methyl, ethyl, propyl, —OH, methoxy, ethoxy, propoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

Q¹ is selected from:

H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃,

C₁₋₄ alkyl substituted with 0-1 R⁸,

C₂₋₃ alkenyl substituted with 0-1 R⁸, and

C₂₋₃ alkynyl substituted with 0-1 R⁸;

Q² is H;

alternatively, Q¹ and Q² can be taken together to form ═O;

R⁷ is selected from

H, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃,

C₁₋₃ alkyl substituted with 0-1 R⁸,

C₂₋₃ alkenyl substituted with 0-1 R⁹,

C₂₋₃ alkynyl substituted with 0-1 R⁹,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹, and

phenyl substituted with 0-2 R⁹;

R⁸ is selected from

methyl, ethyl, propyl, butyl, —OH, methoxy, ethoxy, propoxy, butoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹,

5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, 2-imidazolyl, 1-pyrazolyl, 3-pyrazolyl, and 4-pyrazolyl;

R⁹ is selected from methyl, ethyl, propyl, butyl, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, —OH, methoxy, ethoxy, propoxy, butoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R¹⁴ and R¹⁵ are independently selected from H, methyl, and ethyl;

R¹⁶ is selected from H, OH, methyl, ethyl, methoxy, ethoxy, and NR¹⁴R¹⁵; and

R¹⁷ is selected from methyl, ethyl, methoxy, and ethoxy.

In a further preferred embodiment, a compound of the present invention is of Formula (Ia)

or a pharmaceutically acceptable salt thereof.

In a further preferred embodiment, a compound of the present invention is of Formula (Ib)

or a pharmaceutically acceptable salt thereof.

[5] In a most preferred embodiment, the compound of Formula (I) selected from:

or a pharmaceutically acceptable salt thereof.

[6] In a second embodiment, the present invention provides a novel compound of Formula (I), wherein:

A is O or S;

W is N or CR³;

X is N or CR^(3a);

Y is N or CR^(3b);

Z is N or CR^(3c);

provided that one or two of W, X, Y, and Z are N,

R¹ is C₁₋₃ alkyl substituted with 0-7 halogen;

R² is selected from

C₁₋₆ alkyl substituted with 0-2 R⁴,

C₂₋₅ alkenyl substituted with 0-2 R⁴,

C₂₋₅ alkynyl substituted with 0-1 R⁴,

C₃₋₆ cycloalkyl substituted with 0-2 R⁵,

phenyl substituted with 0-2 R⁵, and

3-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R³ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3a) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3b) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3c) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R⁴ is selected from

C₁₋₆ alkyl substituted with 0-2 R⁵,

C₃₋₁₀ carbocycle substituted with 0-2 R⁵,

phenyl substituted with 0-5 R⁵, and a

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R⁵, at each occurrence, is independently selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

Q¹ and Q² are independently selected from

H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷,

C₁₋₃ alkyl substituted by 3-7 halogens;

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁸, and

C₂₋₆ alkynyl substituted with 0-2 R⁸,

alternatively, Q¹ and Q² can be taken together to form ═O;

alternatively, Q¹ and Q² can be taken together to form:

a 3-6 membered spirocyclic ring, said spirocyclic ring containing 0, 1, or 2 oxygen atoms;

R⁷ is selected from

H,

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁹,

C₂₋₆ alkynyl substituted with 0-1 R⁹,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹, and

C₁₋₃ alkyl substituted by 3-7 halogens;

R⁸ is selected from

C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹,

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; and,

R⁹ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, —SO₂NR¹⁴R¹⁵, and C₁₋₃ alkyl substituted by 3-7 halogens;

R¹⁴ and R¹⁵ are independently selected from H, methyl, ethyl, propyl, and butyl;

R¹⁶ is selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, and NR¹⁴R¹⁵;

R¹⁷ is selected from methyl, ethyl, propyl, methoxy, ethoxy, and propoxy; and

R¹⁸ is selected from methyl, ethyl, propyl, butyl, and phenyl.

[7] In a preferred second embodiment, the present invention provides a novel compound of Formula (I), wherein:

A is O;

W is N or CR³;

X is N or CR^(3a);

Y is N or CR^(3b);

Z is N or CR^(3c);

provided that one or two of W, X, Y, and Z are N,

R¹ is —CF₃, —CF₂CF₃, or —CF₂CF₂CF₃;

R² is selected from

C₁₋₆ alkyl substituted with 0-2 R⁴,

C₂₋₅ alkenyl substituted with 0-2 R⁴,

C₂₋₅ alkynyl substituted with 0-1 R⁴,

C₃₋₆ cycloalkyl substituted with 0-2 R⁵,

phenyl substituted with 0-2 R⁵, and

3-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R³ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3a) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3b) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R^(3c) is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R⁴ is selected from

C₁₋₆ alkyl substituted with 0-2 R⁵,

C₃₋₁₀ carbocycle substituted with 0-2 R⁵,

phenyl substituted with 0-5 R⁵, and a

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵;

R⁵, at each occurrence, is independently selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

Q¹ and Q² are independently selected from

H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷,

C₁₋₃ alkyl substituted by 3-7 halogens;

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁸, and

C₂₋₆ alkynyl substituted with 0-2 R⁸,

alternatively, Q¹ and Q² can be taken together to form ═O;

alternatively, Q¹ and Q² can be taken together to form:

a 3-6 membered spirocyclic ring, said spirocyclic ring containing 0, 1, or 2 oxygen atoms;

R⁷ is selected from

H,

C₁₋₆ alkyl substituted with 0-2 R⁸,

C₂₋₆ alkenyl substituted with 0-2 R⁹,

C₂₋₆ alkynyl substituted with 0-1 R⁹,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹, and

C₁₋₃ alkyl substituted by 3-7 halogens;

R⁸ is selected from

C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹,

5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; and,

R⁹ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, —SO₂NR¹⁴R¹⁵, and C₁₋₃ alkyl substituted by 3-7 halogens;

R¹⁴ and R¹⁵ are independently selected from H, methyl, ethyl, propyl, and butyl;

R¹⁶ is selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, and NR¹⁴R¹⁵;

R¹⁷ is selected from methyl, ethyl, propyl, methoxy, ethoxy, and propoxy; and

R¹⁸ is selected from methyl, ethyl, propyl, butyl, and phenyl.

[8] In a more preferred second embodiment the present invention provides a novel compound of Formula (I), wherein:

R¹ is —CF₃ or —CF₂CF₃;

R² is selected from

C₁₋₃ alkyl substituted with 0-1 R⁴,

C₂₋₃ alkenyl substituted with 0-1 R⁴,

C₂₋₃ alkynyl substituted with 0-1 R⁴,

R³ is selected from methyl, ethyl, —OH, methoxy, ethoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵;

R^(3a) is selected from methyl, ethyl, —OH, methoxy, ethoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵;

R^(3b) is selected from methyl, ethyl, —OH, methoxy, ethoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵;

R^(3c) is selected from methyl, —OH, methoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN;

R⁴ is selected from

cyclopropyl substituted with 0-1 R⁵,

phenyl substituted with 0-3 R⁵, and a

5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-1 R⁵, wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, and 2-imidazolyl;

R⁵, at each occurrence, is independently selected from methyl, ethyl, propyl, —OH, methoxy, ethoxy, propoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

Q¹ and Q² are independently selected from

H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃,

C₁₋₄ alkyl substituted with 0-1 R⁸,

C₂₋₃ alkenyl substituted with 0-1 R⁸, and C₂₋₃ alkynyl substituted with 0-1 R⁸,

alternatively, Q¹ and Q² can be taken together to form ═O;

R⁷ is selected from

H, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃,

C₁₋₃ alkyl substituted with 0-1 R⁸,

C₂₋₃ alkenyl substituted with 0-1 R⁹,

C₂₋₃ alkynyl substituted with 0-1 R⁹,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹, and

phenyl substituted with 0-2 R⁹;

R⁸ is selected from

methyl, ethyl, propyl, butyl, —OH, methoxy, ethoxy, propoxy, butoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵,

C₃₋₆ cycloalkyl substituted with 0-2 R⁹,

phenyl substituted with 0-5 R⁹,

5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, and 2-imidazolyl;

R⁹ is selected from methyl, ethyl, propyl, butyl, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, —OH, methoxy, ethoxy, propoxy, butoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵;

R¹⁴ and R¹⁵ are independently selected from H, methyl, and ethyl;

R¹⁶ is selected from H, OH, methyl, ethyl, methoxy, ethoxy, and NR¹⁴R¹⁵; and

R¹⁷ is selected from methyl, ethyl, methoxy, and ethoxy.

In a third embodiment, the present invention provides a novel pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (I) or (II) or pharmaceutically acceptable salt form thereof.

In a fourth embodiment, the present invention provides a novel method for treating HIV infection which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Formula (I) or (II) or pharmaceutically acceptable salt form thereof.

In a fifth embodiment, the present invention provides a novel method of treating HIV infection which comprises administering, in combination, to a host in need thereof a therapeutically effective amount of:

(a) a compound of Formula (I) or II; and,

(b) at least one compound selected from the group consisting of HIV reverse transcriptase inhibitors and HIV protease inhibitors.

In another preferred embodiment, the reverse transcriptase inhibitor is selected from efavirenz, AZT, ddC, ddI, d4T, 3TC, delavirdine, nevirapine, Ro 18,893, trovirdine, MKC-442, HBY 097, ACT, UC-781, UC-782, RD4-2025, and MEN 10979, and the protease inhibitor is selected from saquinavir, ritonavir, indinavir, amprenavir, nelfinavir, palinavir, BMS-232623, GS3333, KNI-413, KNI-272, LG-71350, CGP-61755, PD 173606, PD 177298, PD 178390, PD 178392, U-140690, and ABT-378.

In an even more preferred embodiment, the reverse transcriptase inhibitor is selected from AZT, efavirenz, and 3TC and the protease inhibitor is selected from saquinavir, ritonavir, nelfinavir, and indinavir.

In a still further preferred embodiment, the reverse transcriptase inhibitor is AZT.

In another still further preferred embodiment, the reverse transcriptase inhibitor is efavirenz.

In another still further preferred embodiment, the protease inhibitor is indinavir.

In a sixth embodiment, the present invention provides a pharmaceutical kit useful for the treatment of HIV infection, which comprises a therapeutically effective amount of:

(a) a compound of Formula (I) or II; and,

(b) at least one compound selected from the group consisting of HIV reverse transcriptase inhibitors and HIV protease inhibitors, in one or more sterile containers.

In a seventh embodiment, the present invention provides a novel method of inhibiting HIV present in a body fluid sample which comprises treating the body fluid sample with an effective amount of a compound of Formula (I) or II.

In a eighth embodiment, the present invention to provides a novel a kit or container comprising a compound of Formula (I) or (II) in an amount effective for use as a standard or reagent in a test or assay for determining the ability of a potential pharmaceutical to inhibit HIV reverse transcriptase, HIV growth, or both.

DEFINITIONS

As used herein, the following terms and expressions have the indicated meanings. It will be appreciated that the compounds of the present invention contain an asymmetrically substituted carbon atom, and may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis, from optically active starting materials. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomer form is specifically indicated.

The processes of the present invention are contemplated to be practiced on at least a multigram scale, kilogram scale, multikilogram scale, or industrial scale. Multigram scale, as used herein, is preferably the scale wherein at least one starting material is present in 10 grams or more, more preferably at least 50 grams or more, even more preferably at least 100 grams or more. Multikilogram scale, as used herein, is intended to mean the scale wherein more than one kilogram of at least one starting material is used. Industrial scale as used herein is intended to mean a scale which is other than a laboratory scale and which is sufficient to supply product sufficient for either clinical tests or distribution to consumers.

The present invention is intended to include all isotopes of atoms occurring on the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium. Isotopes of carbon include C-13 and C-14.

As used herein, “alkyl” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms; for example, “C₁₋₆ alkyl” denotes alkyl having 1 to 6 carbon atoms, ie. methyl, ethyl, propyl, butyl, pentyl, hexyl, and branched isomers therein. Examples of alkyls include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, i-butyl, n-butyl, s-butyl, t-butyl, i-pentyl, n-pentyl, and s-pentyl. “Haloalkyl” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more halogen (for example —C_(v)F_(w) where v=1 to 3 and w=1 to (2v+1)). Examples of haloalkyl include, but are not limited to, trifluoromethyl, trichloromethyl, pentafluoroethyl, pentachloroethyl, heptafluoropropyl, and heptachloropropyl. “Alkoxy” represents an alkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy. “Cycloalkyl” is intended to include saturated ring groups, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. “Alkenyl” is intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon—carbon bonds which may occur in any stable point along the chain, such as ethenyl, 1-methyl-ethenyl, 2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and the like. “Alkynyl” is intended to include hydrocarbon chains of either a straight or branched configuration and one or more triple carbon—carbon bonds which may occur in any stable point along the chain, such as ethynyl, propynyl, 2-propynyl, butynyl, 2-butynyl, 3-butynyl, and the like.

“Halo” or “halogen” as used herein refers to fluoro, chloro, bromo and iodo. “Counterion” is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, sulfate and the like.

As used herein, “aryl” or “aromatic residue” is intended to mean an aromatic moiety containing the specified number of carbon atoms, such as phenyl or naphthyl. As used herein, “carbocycle” or “carbocyclic residue” is intended to mean any stable 3- to 7-membered monocyclic or bicyclic or 7- to 14-membered bicyclic or tricyclic carbon ring, which may be saturated or partially unsaturated. Examples of such carbocycle include, but are not limited to, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, biphenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin).

As used herein, the term “heterocycle” or “heterocyclic system” is intended to mean a stable 5- to 6-membered monocyclic heterocyclic ring which is saturated partially unsaturated or unsaturated (aromatic), and which consists of carbon atoms and from 1 to 3 heteroatoms independently selected from the group consisting of N, O and S. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. If specifically noted, a nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds one, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than one.

As used herein, the term “aromatic heterocyclic system” is intended to mean a stable 5- to 6-membered monocyclic heterocyclic aromatic ring which consists of carbon atoms and from 1 to 3 heteroatoms independently selected from the group consisting of N, O and S. It is preferred that the total number of S and O atoms in the aromatic heterocycle is not more than one.

Examples of heterocycles include, but are not limited to, 2-pyrrolidonyl, 2H-pyrrolyl, 4-piperidonyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, isoxazolyl, morpholinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, tetrahydrofuranyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, and 1,3,4-triazolyl. Preferred heterocycles include, but are not limited to, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, and oxazolidinyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles containing oxygen.

As used herein, “HIV reverse transcriptase inhibitor” is intended to refer to both nucleotide and non-nucleotide inhibitors of HIV reverse transcriptase (RT). Examples of nucleotide RT inhibitors include, but are not limited to, AZT, ddC, ddI, d4T, and 3TC. Examples of non-nucleotide RT inhibitors include, but are no limited to, efavirenz (DuPont Merck), delavirdine (Pharmacia and Upjohn U90152S), nevirapine (Boehringer Ingelheim), Ro 18,893 (Roche), trovirdine (Lilly), MKC-442 (Triangle), HBY 097 (Hoechst), ACT (Korean Research Institute), UC-781 (Rega Institute), UC-782 (Rega Institute), RD4-2025 (Tosoh Co. Ltd.), PNU142721 (Pharmacia and Upjohn), and MEN 10979 (Menarini Farmaceutici).

As used herein, “HIV protease inhibitor” is intended to refer to compounds which inhibit HIV protease. Examples include, but are not limited, saquinavir (Roche, Ro31-8959), ritonavir (Abbott, ABT-538), indinavir (Merck, MK-639), amprenavir (Vertex/Glaxo Wellcome), nelfinavir (Agouron, AG-1343), palinavir (Boehringer Ingelheim), BMS-232623 (Bristol-Myers Squibb), GS3333 (Gilead Sciences), KNI-413 (Japan Energy), KNI-272 (Japan Energy), LG-71350 (LG Chemical), CGP-61755 (Ciba-Geigy), DMP450 (DuPont Merck), PD 173606 (Parke Davis), PD 177298 (Parke Davis), PD 178390 (Parke Davis), PD 178392 (Parke Davis), U-140690 (Pharmacia and Upjohn), and ABT-378. Additional examples include the cyclic protease inhibitors disclosed in WO 93/07128, WO 94/19329, WO 94/22840, and PCT Application Number US96/03426.

As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.

The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the disclosure of which is hereby incorporated by reference.

The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit/risk ratio.

“Prodrugs” are intended to include any covalently bonded carriers which release the active parent drug according to Formula (I) or other formulas or compounds of the present invention in vivo when such prodrug is administered to a mammalian subject. Prodrugs of a compound of the present invention, for example Formula (I), are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of the present invention wherein the hydroxy or amino group is bonded to any group that, when the prodrug is administered to a mammalian subject, cleaves to form a free hydroxyl or free amino, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of the present invention, and the like.

“Stable compound” and “stable structure” are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. Only stable compounds are contempleted by the present invention.

“Substituted” is intended to indicate that one or more hydrogens on the atom indicated in the expression using “substituted” is replaced with a selection from the indicated group(s), provided that the indicated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., ═O) group, then 2 hydrogens on the atom are replaced.

“Therapeutically effective amount” is intended to include an amount of a compound of the present invention or an amount of the combination of compounds claimed effective to inhibit HIV infection or treat the symptoms of HIV infection in a host. The combination of compounds is preferably a synergistic combination. Synergy, as described for example by Chou and Talalay, Adv. Enzyme Regul. 22:27-55 (1984), occurs when the effect (in this case, inhibition of HIV replication) of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at suboptimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased antiviral effect, or some other beneficial effect of the combination compared with the individual components.

SYNTHESIS

The compounds of the present invention can be prepared in a number of ways well known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. Preferred methods include but are not limited to those methods described below. Each of the references cited below are hereby incorporated herein by reference. In the Schemes which follow: R¹ is shown as a CF₃ group, but could be any one of the presently described R¹ groups; G represents R³, R^(3a), R^(3b), or R^(3c) or any combination of these groups.

Scheme 1 illustrates a method for the preparation of 4,4-disubstituted quinolin-2-ones, 6, starting with an appropriately substituted 2-amino-trifluoromethylketone, 1. Acylation with bromoacetyl bromide followed by the treatment of the halide by benzene sulfinate provides for a ring closed compound in one step via displacement followed by ring closure. Acylation of the tertiary alcohol, 3, followed by elimination by base provides for a sulfone of formula 4. This compound can be reacted readily with organometallics to introduce the R² group. Lastly the sulfone moiety, 5, can be reductively removed, for example, by using aluminum amalgam.

Scheme 1a illustrates a method, analogous to Scheme 1, of making derivatives to tetrahydroquinolinone compounds of formula 6 wherein W, X, Y and/or Z are nitrogen; for example, tetrahydronaphthyridinones, tetrahydropyrido[3,4-b]-pyridinones, tetrahydropyrido[3,2-b]-pyridinones, and tetrahydropyrido[4,3-b]-pyridinones. An appropriately substituted amino-ketone 1n can be acylated and the resulting amide cyclized in the presence of benzenesulfinate to give alcohol 3n. Dehydration with base provides the α,β-unsaturated ketone 4n which can be modified via a lithium or grignard reagent to give 5n. Sulfone reduction can be achieved with Al/Hg or other known methods of reduction to provide 6n.

Scheme 2 illustrates methodology for the introduction of alkyl groups, Q¹, onto the C-3 carbon of the quinolin-2-ones. Treatment of the protected compound of formula 7 with base followed by a variety of alkylating agents, Q¹X, provides the protected compounds, 8, which can subsequently be deprotected using acidic reaction conditions to provide compounds 9.

Alternatively, alkyl groups can also be introduced using an earlier intermediate in the synthetic sequence. Compound of formula 10 can be treated with base followed by an alkylating agent. The product upon treatment with aluminum amalgam for the removal of the sulfone functionality followed by deprotection provides compounds of formula 9.

In a manner analogous to that of Scheme 1,4,4-disubstituted quinolin-2-ones bearing a carboalkoxy group at the C-3 position can be prepared as illustrated in Scheme 4. Treatment with methyl malonylchloride under basic conditions ensures not only acylation but ring closure as well. Acylation of the tertiary alcohol followed by elimination provided compounds of formula 15. Protection of the amide moiety followed by the addition of organometallics provides compounds of formula 17. Deprotection of the amide functionality provided compounds of formula 18.

Scheme 5 illustrates methodology for the introduction of oxygen bearing moiety at the C-3 position of the 4,4-disubstituted quinolin-2-ones. Treatment of an appropriately protected quinolinone with base followed by an agent such as MOOPH allows for the introduction of the hydroxyl functionality.

Scheme 6 illustrates methodology for the introduction of nitrogen bearing moiety at the C-3 position of the 4,4-disubstituted quinolin-2-ones. Treatment of an appropriately protected quinolinone with base followed by an agent such as tosyl azide allows for the transfer of the azide group onto the C-3 position which can be subsequently reduced to an amine by routes such as the those represented by the Staudinger reaction

Scheme 7 illustrates a method of reducing acetylenes to cis-olefins using NH₂OSO₃H and DIPEA. The conversion of the acetylenes to cis-olefins could also be effected by treatment with Raney Nickel and hydrazine. Trans-olefins are available by methods known to one of skill in the art for isomerization of the cis-olefins. Other methods known to reduce alkynes to alkenes could also be used.

Thioamides of the present invention can be formed as shown in Scheme 8 from their corresponding amides. The amide is initially converted into a halo-imine via a chlorinating agent such as POCl₃ which is then further transformed into a thioamide with NH₂C(S)NH₂.

Scheme 9 describes a means of obtaining an amino-ketone used as described above. After iodination of an appropriate aniline, the trifluoromethyl group can be introduced using a strong base and ethyl trifluoroacetate. Alternatively, Scheme 9 describes a means for obtaining an amino-ketone wherein R¹ could be any one of the presently described R¹ alkyls groups in addition to trifluoromethyl, for example, pentafluoroethyl, pentachloroethyl, heptafluoropropyl, etc, by using the appropriate ethyl haloaklylacetate in the above reaction.

Scheme 9A describes an alternate route to ketone substituted anilines from a substituted aniline, wherein the aniline is protected, ester addition is accomplished using a strong base and the amine protecting group is subsequently removed.

In addition to the methods of obtaining keto-anilines described previously, nucleophilic opening of isatoic anhydrides can also be used as shown in Scheme 10. This reaction is accomplished by using an anionic nucleophile of the group R^(1a). See Mack et al, J. Heterocyclic Chem. 1987, 24, 1733-1739; Coppola et al, J. Org. Chem. 1976, 41(6), 825-831; Takimoto et al, Fukuoka Univ. Sci. Reports 1985, 15(1), 37-38; Kadin et al, Synthesis 1977, 500-501; Staiger et al, J. Org. Chem. 1959, 24, 1214-1219.

One enantiomer of a compound of Formula (I) may display superior activity compared with the other. Thus, the following stereochemistries are considered to be a part of the present invention.

When required, separation of the racemic material can be achieved by HPLC using a chiral column as exemplified in Examples 27-34 (Scheme 4) or by a resolution using a resolving agent such as camphonic chloride as in Thomas J. Tucker, et al, J. Med. Chem. 1994, 37, 2437-2444. A chiral compound of Formula (I) may also be directly synthesized using a chiral catalyst or a chiral ligand, e.g. Mark A. Huffman, et al, J. Org. Chem. 1995, 60, 1590-1594.

Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments which are given for illustration of the invention and are not intended to be limiting thereof.

EXAMPLES

Abbreviations used in the Examples are defined as follows: “° C” for degrees Celsius, “d” for doublet, “dd” for doublet of doublets, “eq” for equivalent or equivalents, “g” for gram or grams, “mg” for milligram or milligrams, “mL” for milliliter or milliliters, “H” for hydrogen or hydrogens, “hr” for hour or hours, “m” for multiplet, “M” for molar, “min” for minute or minutes, “MHz” for megahertz, “MS” for mass spectroscopy, “nmr” or “NMR” for nuclear magnetic resonance spectroscopy, “t” for triplet, “TLC” for thin layer chromatography, “Al/Hg” for aluminum amalgam, “Ac₂O” for acetic anhydride, “ACN” for acetonitrile, “(BOC)₂O” for di-tert-butyl dicarbonate, “CAN” for ceric ammonium nitrate, “CDI” for carbonyl diimidazole, “cycPr” for cyclopropyl, “DIPEA” for diisopropylethylamine, “DMAP” for dimethylaminopyridine, “DME” for dimethoxyethane, “EDAC” for 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, “LAH” for lithium aluminium hydride, “LDA” for lithium diisopropylamide, “MOOPH” for oxo-diperoxy-molybdenum(pyridine)(hexamethylphosphoric triamide), “PMBCl” for 4-methoxybenzyl chloride, “SEMCl” for 2-(trimethylsilyl)-ethoxymethyl chloride, “TBAF” for tetrabutylammonium fluoride, “TBS-Cl” for t-butyldimethylsilyl chloride, and “TEA” for triethylamine.

Example 1 6-Chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-4-(trifluoromethyl)-2(1H)-quinalinone

Step A: Preparation of Compound of Formula 2 Wherein G=Cl

To a solution of amino ketone of formula 1 (3.02 g, 13.54 mmol) in THF (55 mL) at room temperature was added potassium carbonate (4.67 g, 33.85 mmol) followed by bromoacetyl bromide (1.5 mL, 16.93 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 3 hours. The reaction mixture was poured onto water and extracted with ethyl acetate (3×100 mL). The combined ethyl acetate extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo to provide compound of formula 2 as a yellow oil. This product was used in the next step of the synthetic sequence without further purification.

Step B: Preparation of Compound of Formula 3 Wherein G=Cl

To a solution of the bromide of formula 2 (crude product, 13.54 mmol) in DMF (55 mL) at room temperature was added sodium benzenesulfinate (4.44 g, 27.08 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 18 hours. The reaction mixture was poured onto water and extracted with ethyl acetate (3×100 mL). The combined ethyl acetate extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. The residue is triturated with hexanes (1 L) and dried in vacuo to provide 4.88 g of compound of formula 3, (5.49 g theoretical, 89%). ¹H NMR (300 MHz, DMSO-d₆) δ 11.0(br s, 1H), 7.96(s, 1H), 7.76(d, 2H, J=8 Hz), 7.66(m, 1H), 7.51(m, 2H), 7.44(s, 1H), 7.33(m, 1H), 6.82(d, 1H, J=8 Hz), 4.47(s, 1H). ¹⁹F NMR (282 MHz, DMSO-d₆) δ −80.99(s, 3F). High resolution mass spec: calculated for C₁₆H₁₁NO₄F₃ClS(M+H)⁺: 405.0042, found 405.0049.

Step C: Preparation of Compound of Formula 4 Wherein G=Cl

To a slurry of the tertiary alcohol of formula 3 (6.815 g, 16.83 mmol) in methylene chloride (100 mL) at room temperature was added 4-(dimethylamino)pyridine (4.11 g, 33.65 mmol) followed by acetic anhydride (3.5 mL, 37.03 mmol) and the resulting reaction mixture is allowed to stir at room temperature for 18 hours. The reaction mixture was poured onto water and extracted with ethyl acetate (3×100 mL). The ethyl acetate extracts were washed with saturated NaHCO₃ and dried over anhydrous Na₂SO₄ and concentrated in vacuo. The residue is triturated with hexanes (1 L) and dried in vacuo to provide 6.06 g of compound of formula 4, (6.51 g theoretical, 93%). Anal. (C₁₆H₉NO₃F₃ClS) Calcd. C, 49.56; H, 2.349; N, 3.61; Cl, 9.14; F, 14.70; S, 8.279; Found. C, 49.26; H, 2.68; N, 3.30; Cl, 9.23; F, 14.49; S, 8.13.

Step D: Preparation of Compound of Formula V Wherein G=Cl, R¹=Cyclopropylacetylene

To a solution of cyclopropylacetylene (153 μL, 1.16 mmol) in THF (4 mL) at 0° C. was added nBuLi (0.65 mL, 1.04 mmol) and the resulting reaction mixture was allowed to stir at 0° C. for 30 minutes. Thereafter the reaction mixture was cannulated to stirred solution of sulfone of formula 4 (100 mg, 0.26 mmol) in THF (2 mL) at −78° C. The dry ice bath is removed and the reaction mixture is stirred for an additional hour. The reaction mixture is poured onto saturated NH₄Cl and extracted with ethyl acetate (3×25 mL) and the combined ethyl acetate extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 30% EtOAc-hexanes eluant) provided 33 mg of compound of formula 5, (117 mg theoretical, 28%). ¹H NMR (300 MHz, CDCl₃) δ 9.2(br s, 1H), 7.9(m, 1H), 7.65(m, 1H), 7.55(m, 2H), 7.45(m, 2H), 7.25(m, 1H), 6.8(m, 1H), 4.45(s, 1H), 1.4(m, 1H), 0.9(m, 4H). High resolution mass spec: calculated for C₂₁H₁₆NO₃F₃SCl (M+H)⁺: 454.0492; found: 454.0475.

Step E:

To a solution of sulfone of formula 5 (29 mg, 0.044 mmol) in THF:water (9:1, 2 mL) at room temperature was added Al/Hg amalagam (prepared from aluminum foil (230 mg) and HgCl₂ (1.5 g) in water (30 mL) and the resulting reaction mixture was allowed to stir at reflux for one hour. The reaction mixture was filtered through Celite and the filterate concentrated in vacuo. Chromatography (SiO₂, 30% EtOAc-hexanes eluant) provided 11 mg of the title compound, (13.8 mg theoretical, 80%). ¹H NMR (300 MHz, CDCl₃) δ 8.95(br s, 1H), 7.65(m, 1H), 7.3(m, 1H), 6.8(m, 1H), 3.0(dd, J=17 Hz, 17 Hz, 2H), 1.35(m, 1H), 0.9(m, 4H). ¹⁹F NMR (282 MHz, CDCl₃) δ −76.66(s, 3F). Anal. (C₁₅H₁₁NOF₃Cl) Calcd. C, 57.43; H, 3.53; N, 4.475; F, 18.17; Cl, 11.30; Found. C, 57.40; H, 3.44; N, 4.34; F, 17.92; Cl, 11.36.

Example 2 6-Chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-3-methoxycarbonyl-4-(trifluoromethyl)-2(1H)-quinalinone

Step A: Preparation of Compound of Formula 14 Wherein G=Cl and R²=Methyl

To a solution of amino-ketone 1 (5.2 g, 23.32 mmol) in DMF (100 mL) at room temperature was added K₂CO₃ (8.045 g, 58.3 mmol) followed by methyl malonylchloride (3.14 mL, 29.15 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 4 hours. The reaction mixture was poured onto water and extracted with EtOAc (3×100 mL) and the combined EtOAc extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. The residue was triturated with hexanes to provide 14.63 g compound of formula 14, (15.06 g theoretical, 96%). ¹H NMR (300 MHz, DMSO-d₆) d 10.92(br s, 1H), 7.8(br s, 1H), 7.5(m, 1H), 7.4(m, 1H), 6.95(m, 1H), 3.58(s, 3H), 3.8(s, 1H). ¹⁹F NMR (282 MHz, DMSO-d₆) δ −81.69(s, 3F). Anal. (C₁₂H₉NO₄F₃Cl) Calcd. C, 44.53; H, 2.80; N, 4.337; F, 17.61; Cl, 10.95; Found. C, 44.51; H, 2.99; N, 4.19; F, 17.354; Cl, 11.15.

Step B: Preparation of Compound of Formula 15 Wherein G=Cl and R²=Methyl

To a solution of of compound of formula 14 (14.58 g, 45.14 mmol), in CH₂Cl₂ (200 mL) at room temperature was added DMAP (11.015 g, 90.28 mmol) followed by Ac₂O (9.4 mL, 99.31 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 14 hours. The reaction mixture was poured onto 10% citric acid and extracted with CH₂Cl₂ (3×100 mL) and the combined CH₂Cl₂ extracts were washed with saturated NaHCO₃, dried over anhydrous Na₂SO₄ and concentrated in vacuo to provide 13.32 g of compound of formula 15, 13.77 g, theoretical, 97%). ¹H NMR (300 MHz, DMSO-d₆) δ 12.94(br s, 1H), 7.8(m, 1H), 7.65(m, 1H), 7.45(m, 1H), 3.83(s, 3H). ¹⁹F NMR (282 MHz, DMSO-d₆) δ −59.15(s, 3F). Anal. (C₁₂H₇NO₃F₃Cl) Calcd. C, 47.16; H, 2.318; N, 4.58; F, 18.65; Cl, 11.60; Found. C, 47.22; H, 2.36; N, 4.57; F, 18.29; Cl, 11.85.

Step C: Preparation of Compound of Formula 16 Wherein G=Cl and R²=Methyl

To a solution of compound of formula 15 (10 mg, 0.32 mmol) in DMF (2 mL) at room temperature was added Ag₂CO₃ (265 mg, 0.96 mmol) followed by PMBCl (57 μL, 0.42 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 14 hours. The reaction mixture was filtered through Celite and the filterate washed with water. The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 10% EtOAc-hexanes eluant) provided 105 mg of compound of formula 16, (136 mg theoretical, 77%). ¹H NMR (300 MHz, CDCl₃) δ 8.0(m, 1H), 7.85(M, 1H), 7.65(m, 1H), 7.4(d, J=9 Hz, 2H), 6.9(d, J=9 Hz, 2H), 5.5(s, 2H), 9.95(s, 3H), 3.8(s, 3H). ¹⁹F NMR (282 MHz, CDCl₃) δ −58.37(s, 3F).

Step D: Preparation of Compound of Formula 17 Wherein G=Cl, R¹=Cyclopropylacetylene and R²=Methyl

To a solution of cyclopropylacetylene (565 μL, 4.28 mmol) in THF (12 mL) at 0° C. was added nBuLi (2.38 mL, 3.8 mmol) and the resulting reaction mixture was allowed to stir at 0° C. for 30 minutes. Thereafter the reaction mixture was cannulated to stirred solution of sulfone of formula 16 (405 mg, 0.95 mmol) in THF (6 mL) at −78° C. The dry ice bath is removed and the reaction mixture is stirred for an additional hour. The reaction mixture is poured onto saturated NH₄Cl and extracted with ether (3×25 mL) and the combined ether extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 15% CH₂Cl₂-hexanes eluant) provided 220 mg of compound of formula 17, (465 mg theoretical, 47%). ¹H NMR (300 MHz, CDCl₃) δ 7.8(m, 1H), 7.35(m, 2H), 7.2(d, J=9 Hz, 2H), 6.85(d, J=9 Hz, 2H), 5.3(dd, J=10, 12 Hz, 2H), 3.8(s, 3H), 3.6(s, 3H), 1.35(m, 1H), 0.9(m, 2H), 0.75(m, 2H). ¹⁹F NMR (282 MHz, CDCl₃) δ −77.03(s, 3F). Mass spec. (-ES): 490(M−H)⁺ (80%), 370 (100%).

Step E:

To a solution of PMB protected quinolinone of formula 17 (30 mg, 0.061 mmol) in ACN:water (9:1, 1 mL) at room temperature was added CAN (167 mg, 0.3 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 30 minutes. The reaction mixture was poured onto water and extracted with EtOAc (3×25 mL) and the combined EtOAc extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 20% EtOAc-hexanes eluant) provided 20 mg of the title compound, (22 mg theoretical, 91%). ¹H NMR (300 MHz, CDCl₃) δ 9.12(br s, 1H), 7.6(m, 1H), 7.35(m, 1H), 6.6(m, 1H), 4.0(s, 2H), 3.75(s, 3H), 1.35(m, 1H), 0.85(m, 2H), 0.75(m, 2H). ¹⁹F NMR (282 MHz, CDCl₃) δ −76.22(s, 3F). High resolution mass spec: calculated for C₁₆H₁₃NOF₃Cl(M−H)⁺: 370.0458, found 370.0473.

Example 3 6-Chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-3-methyl-4-(trifluoromethyl)-2(1H)-quinalinone

Step A: Preparation of Compound of Formula 10 Wherein G=Cl

To a solution of quinolinone of formula 4 (4.12 g, 10.6 mmol) in DMF (40 mL) at room temperature was added DIPEA (3.15 mL, 18 mmol) followed by SEMCl (2.26 mL, 12.8 mmol) and the resulting reaction mixture is allowed to stir at room temperature for 14 hours. The reaction mixture was poured onto 1N HCl and extracted with ether (2×100 mL) and the combined ether extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 15% EtOAc-hexanes eluant) provided 5.47 g of compound of formula 10, (5.49 g theoretical, 83%). ¹H NMR (300 MHz, CDCl₃) δ 8.25(m, 2H), 8.05(m, 1H), 7.75-7.55(m, 5H), 5.65(s, 2H), 3.53(t, J=8 Hz, 2H), 0.91(t, J=8 Hz, 2H), 0.01(s, 9H). ¹⁹F NMR (282 MHz, CDCl₃) δ −51.70(s, 3F). Mass spec. (NH₃-CI): 518(M+H)⁺ (100%).

Step B: Preparation of Compound of Formula 11 Wherein G=Cl, R¹=Cyclopropylacetylene

To a solution of cyclopropylacetylene (232 μL, 1.76 mmol) in THF (6 mL) at 0° C. was added nBuLi (0.98 mL, 1.56 mmol) and the resulting reaction mixture was allowed to stir at 0° C. for 30 minutes. Thereafter the reaction mixture was cannulated to stirred solution of sulfone of formula 10 (200 mg, 0.39 mmol) in THF (3 mL) at −78° C. The dry ice bath is removed and the reaction mixture is stirred for an additional hour. The reaction mixture is poured onto saturated NH₄Cl and extracted with ether (3×25 mL) and the combined ether extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 30% EtOAc-hexanes eluant) provided 153 mg of compound of formula 11, (228 mg theoretical, 67%). ¹H NMR (300 MHz, CDCl₃) δ 7.85(m, 2H), 7.65(m, 2H), 7.5(m, 2H),7.35(m, 2H), 5.59(d, J=11 Hz, 1H), 4.94(d, J=11 Hz, 1H), 4.6(s, 1H), 3.75(m, 1H), 3.6(m, 1H), 1.3(m, 1H), 0.95(m, 2H), 0.85(m, 4H), 0.00(s, 9H). Mass spec. (ES-): 582(M−H)⁺ (100%).

Step C: Preparation of Compound of Formula 12 Wherein G=Cl, R¹=Cyclopropylacetylene and R²=Methyl

To a solution of sulfone-quinolinone of formula 11 (153 mg, 0.26 mmol) in DMF (1.5 mL) at room temperature was added K₂CO₃ (180 mg, 1.3 mmol) followed by methyl iodide (40 μl, 0.65 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 14 hours. The reaction mixture is poured onto water and extracted with ether (3×50 mL) and the combined ether extracts were dried over anhydrous MgSO₄ and concentrated in vacuo. Chromatography (Sio₂, 10% EtOAc-hexanes eluant) provided 111 mg of compound of formula 12 as mixture of diastreomers, (155 mg theoretical, 72%). ¹H NMR (300 MHz, CDCl₃) δ 8.4(m, 2H), 8.0(m, 1H), 7.9-7.4(m, 13H), 5.8(d, J=11 Hz, 1H), 5.6(d, J=11 Hz, 1H), 5.1(d, J=11 Hz, 1H), 5.0(d, J=11 Hz, 1H), 4.0-3.6(m, 6H), 2.2(m, 3H), 1.8(s, 3H), 1.6(m, 1H), 1.05-0.85(m, 13H), 0.2(s, 9H), 0.00(s, 9H). ¹⁹F NMR (282 MHz, CDCl₃) δ −60.95(s, 3F, 35%), −66.65 (s, 3F, 100%). Mass spec. (NH₃-CI): 615(M+NH₄ ⁺, 100%).

Step D: Preparation of Compound of Formula 13 Wherein G=Cl, R¹=Cyclopropylacetylene and R²=Methyl

To a solution of sulfone of formula 12 (111 mg, 0.19 mmol) in THF:water (9:1, 2.5 mL) at room temperature was added Al/Hg amalagam (prepared from aluminum foil (160 mg) and HgCl₂ (1 g) in water (25 mL) and the resulting reaction mixture was allowed to stir at reflux for two hours. The reaction mixture was filtered through Celite and the filterate concentrated in vacuo. Chromatography (SiO₂, 10% EtOAc-hexanes eluant) provided 36 mg of compound of formula 13, (87 mg theoretical, 41%). ¹H NMR (300 MHz, CDCl₃) δ 7.7(m, 1H), 7.4(m, 2H), 5.65(d, J=11 Hz, 1H), 5.0(d, J=11 Hz, 1H), 3.6(m, 2H), 3.0(m, 1H), 1.6(m, 3H), 1.4(m, 1H), 0.95(m, 2H), 0.9(m, 2H), 0.8(m, 2H), 0.00(s, 9H). ¹⁹F NMR (282 MHz, CDCl₃) δ −69.53(s, 3F). Mass spec. (NH₃-CI): 458(M+H)⁺ (42%), 430 (100%), 328 (M−SEM+H⁺, 47%).

Step E:

To a solution of SEM protected quinolinone of formula 13 (36 mg, 0.079 mmol) in CH₂Cl₂ (1 mL) was added TFA (1 mL) and the resulting reaction mixture was allowed to stir at room temperature for 20 minutes. The reaction mixture was poured onto saturated NaHCO₃ and extracted with CH₂Cl₂ (3×25 mL) and the combined CH₂Cl₂ extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. The residue was taken up in MeOH (1 mL) and 15% NaOH (1 mL) was added to the reaction, and the resulting reaction mixture was allowed to stir at room temperature for 10 minutes. The reaction mixture was poured onto water and extracted with CH₂Cl₂ (3×25 mL) and the combined CH₂Cl₂ extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 20% EtOAc-hexanes eluant) provided 14 mg of the title compound, (26 mg theoretical, 53%). ¹H NMR (300 MHz, CDCl₃) δ 8.65(br s, 1H), 7.7(m, 1H), 7.3(m, 1H), 6.8(m, 1H), 3.0(m, 1H), 1.55(m, 3H), 1.4(m, 1H), 0.9(m, 2H), 0.8(m, 2H). ¹⁹F NMR (282 MHz, DMSO-d₆) δ −69.59(s, 3F). High resolution mass spec: calculated for C₁₆H₁₃NOF₃Cl(M+H)⁺: 328.0716, found 328.0706.

Example 4 3-Allyl-6-chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-4-(trifluoromethyl)-2(1H)-quinalinone

Step A: Preparation of Compound of Formula 7 Wherein G=Cl and R¹=Cyclopropylacetylene

To a solution of quinolinone of formula 6 (600 mg, 1.92 mmol) in ACN (6 mL) at room temperature was added DMAP (350 mg, 2.88 mmol) followed by (BOC)₂O (1050 mg, 4.81 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 2 hours. The reaction mixture was poured onto 10% citric acid and extracted with EtOAc (2×50 mL) and the combined EtOAc extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 5 to 10% EtOAc-hexanes eluant) provided 730 mg of compound of formula 7, (792 mg theoretical, 92%). ¹H NMR (300 MHz, CDCl₃) δ 7.7(m, 1H), 7.35(m, 1H), 6.9(m, 1H), 3.1(dd, J=17 Hz, 17 Hz, 2H), 1.6(s, 9H), 1.35(m, 1H), 0.85(m, 2H), 0.75(m, 2H). ¹⁹F NMR (282 MHz, CDCl₃) δ −75.91 s, 3F). High resolution mass spec: calculated for C₂₀H₁₈N₂O₃F₃ (M+H)⁺: 412.0927; found: 412.0950.

Step B: Preparation of Compound of Formula 8 Wherein G=Cl and R¹=Cyclopropylacetylene and R²−Allyl

To a solution of the BOC protected quinolinone of formula 7 (90 mg, 0.22 mmol) in DMF 92 mL) at room temperature was added ^(t)BuOK in THF (0.33 mL, 0.33 mmol) followed by allyl iodide (40 μL, 0.44 mmol) and the resulting reaction mixture was allowed to stir at room temperature for 24 hours. The reaction mixture was poured onto water and extracted with EtOAc (2×50 mL) and the combined EtOAc extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 10% EtOAc-hexanes eluant) provided 56 mg of compound of formula 8, (100 mg theoretical, 56%). ¹H NMR (300 MHz, CDCl₃) δ 7.75(m, 1H), 7.3(m, 1H), 6.85(m, 1H), 5.7(m, 1H), 5.0(m, 1H), 3.2-2.7(m, 1H), 2.1(m, 1H), 1.55(s, 9H). 1.4(m, 1H), 0.85(m, 2H), 0.8(m, 2H). ¹⁹F NMR (282 MHz, CDCl₃) δ −75.18(s, 3F).

Step C:

To a solution of quinolinone of formula 8 (56 mg, 0.12 mmol) in CH₂Cl₂ (2 mL) at room temperature was added TFA (2 mL) at room temperature and the resulting reaction mixture was allowed to stir at room temperature for 15 minutes. The reaction mixture was poured onto saturated NaHCO₃ and extracted with EtOAc (2×50 mL) and the combined EtOAc extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 25% EtOAc-hexanes eluant) provided 31 mg of title compound, (42 mg theoretical, 74%). ¹H NMR (300 MHz, CDCl₃) δ 8.85(br s, 1H), 7.6(m, 1H), 7.3(m, 1H), 6.8(m, 1H), 5.75(m, 1H), 5(m, 2H), 2.95(m, 1H), 2.8(m, 1H), 2.15(m, 1H), 1.4(m, 1H), 0.9(m, 4H). ¹⁹F NMR (282 MHz, CDCl₃) δ −75.68(s, 3F). High resolution mass spec: calculated for C₁₈H₁₆NOF₃Cl (M+H)⁺: 354.0873; found: 354.0861.

Example 5 6-Chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-3-phenylmethyl-4-(trifluoromethyl)-2(1H)-quinalinone

The title compound was prepared in a manner similar to the product of Example 4, except that in Step B benzyl bromide was used instead of allyl iodide: ¹H NMR (300 MHz, CDCl₃) δ 9.69(br s, 1H), 7.6(m, 1H), 7.2(m, 1H), 7.15(m, 5H), 6.4(m, 1H), 3.4(m, 1H), 3.15(m, 1H), 2.65(m, 1H), 1.45(m, 1H), 0.9(m, 4H). ¹⁹F NMR (282 MHz, CDCl₃) δ −75.46(s, 3F). High resolution mass spec: calculated for C₂₂H₁₆NOF₃Cl (M−H)⁺: 402.0872; found: 402.0846.

Example 6 6-Chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-3-isopropyl-4-(trifluoromethyl)-2(1H)-quinalinone

The title compound was prepared in a manner similar to the product of Example 4, except that in Step B isopropyl iodide was used instead of allyl iodide: ¹H NMR (300 MHz, CDCl₃) δ 8.4(br s, 1H), 7.65(m, 1H), 7.25(m, 1H), 6.65(m, 1H), 2.8(m, 1H), 2.6(m, 1H), 1.4(m, 1H), 1.2(d, J=7 Hz, 3H), 0.9(m, 2H), 0.8(m, 2H), 0.6(d, J=7 Hz, 3H). ¹⁹F NMR (282 MHz, CDCl₃) δ −76.13(s, 3F). High resolution mass spec: calculated for C₁₈H₁₇NOF₃Cl (M+H)⁺: 356.1029; found: 356.1016.

Example 7 5,6-Difluoro-4-(2-cyclopropylethynyl)-3,4-dihydro-4-(trifluoromethyl)-2(1H)-quinalinone

The title compound was prepared in a manner similar to the product of Example 1, except that in Step A 3,4-difluoro-2-trifluoroacetylaniline was used instead of 4-chloro-2-trifluoroacetylaniline: ¹H NMR (300 MHz, DMSO-d₆) δ 10.6(br s, 1H), 7.45(m, 1H), 6.75(m, 1H), 3.35(d, J=17 Hz, 1H), 2.8(d, J=17 Hz, 1H), 1.4(m, 1H), 0.8(m, 2H), 0.6(m, 2H). ¹⁹F NMR (282 MHz, DMSO-d₆) δ −76.48(s, 3F), −134.81(s, 1F), −145.76(s, 1F). High resolution mass spec: calculated for C₁₅H₁₁NOF₅ (M−H)⁺: 316.0739; found: 316.0760.

Example 8

6-Chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-3-hydroxy-4-(trifluoromethyl)-2(1H)-quinalinone

Step A: Preparation of Compound of Formula 19 Wherein G=Cl and R¹=Cyclopropylacetylene

To a solution of sulfone of formula 11 (123 mg, 0.21 mmol) in THF:water (9:1, 2.5 mL) at room temperature was added Al/Hg amalagam (prepared from aluminum foil (160 mg) and HgCl₂ (1 g) in water (20 mL) and the resulting reaction mixture was allowed to stir at reflux for one hour. The reaction mixture was filtered through Celite and the filterate concentrated in vacuo. Chromatography (SiO₂, 10% EtOAc-hexanes eluant) provided 72 mg of compound of formula 19, (93 mg theoretical, 77%). ¹H NMR (300 MHz, CDCl₃) δ 7.7(m, 1H), 7.4(m, 2H), 5.6(d, J=11 Hz, 1H), 5.1(d, J=11 Hz, 1H), 3.6(m, 2H), 3.15(m, 1H), 1.4(m, 1H), 0.95(m, 2H), 0.9(m, 2H), 0.85(m, 2H), 0.01(s, 9H). ¹⁹F NMR (282 MHz, CDCl₃) δ −76.15(s, 3F). Mass spec. (NH₃-CI): 444(M+H)⁺, 30%), 416 (100%).

Step B: Preparation of Compound of Formula 20 Wherein G=Cl and R¹=Cyclopropylacetylene

To a solution of formula 19 (118 mg, 0.27 mmol) in THF (2 mL) at 0° C. was added LDA (0.2 mL, 0.4 mmol) followed by MoOPH (155 mg, 0.37 mmol) and the resulting reaction mixture was allowed to stir at room temperature (ice bath removed after the addition of reagents) for 14 hours. The reaction mixture was poured onto water and extracted with EtOAc (3×25 mL) and the combined EtOAc extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 5-20% EtOAc-hexanes eluant) provided 66 mg of compound of formula 20 as a mixture of isomers, (124 mg theoretical, 54%). ¹H NMR (300 MHz, CDCl₃) δ 7.65(m, 1H), 7.4(m, 1H), 5.5(d, J=11 Hz, 1H), 5.25(m, J=11 Hz, 1H), 4.45(m, 1H), 3.65(m, 2H), 1.25(m, 1H), 0.95(m, 1H), 0.8(m, 2H), 0.65(m, 2H), 0.01(s, 9H). ¹⁹F NMR (282 MHz, CDCl₃) δ −69.64(s, 3F). High resolution mass spec: calculated for C₂₁H₂₆NO3F₃ClSi(M+H)⁺: 460.1323, found 460.1305.

Step C:

To a solution of SEM protected quinolinone of formula 20 (23 mg, 0.05 mmol) in CH₂Cl₂ (2 mL) was added TFA (2 mL) and the resulting reaction mixture was allowed to stir at room temperature for 20 minutes. The reaction mixture was poured onto saturated NaHCO₃ and extracted with CH₂Cl₂ (3×25 mL) and the combined CH₂Cl₂ extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. The residue was taken up in MeOH (2 mL) and 15% NaOH (2 mL) was added to the reaction, and the resulting reaction mixture was allowed to stir at room temperature for 10 minutes. The reaction mixture was poured onto water and extracted with CH₂Cl₂ (3×25 mL) and the combined CH₂Cl₂ extracts were dried over anhydrous Na₂SO₄ and concentrated in vacuo. Chromatography (SiO₂, 40% EtOAc-hexanes eluant) provided 5 mg of the title compound as a mixture of isomers, (16 mg theoretical, 31%). ¹H NMR (300 MHz, CDCl₃) 68.2(br s, 1H), 7.6(m, 1H), 7.35(m, 1H), 6.6(m, 1H), 4.45 (m, 1H), 3.45 (m, 1H), 1.3 (m, 1H), 0.85 (m, 2H), 0.75 (m, 2H). ¹⁹F NMR (282 MHz, CDCl₃) δ −70.75(s, 3F). High resolution mass spec: calculated for C₁₅H₁₂NO₂F₃Cl (M+H)⁺: 330.0508, found 330.0495.

Table 1 *

Ex.# G R¹ R² Q¹ (M + H)⁺ 1 6-Cl —CF₃ —C≡C-cycPr —H 314.0559 2 6-Cl —CF₃ —C≡C-cycPr —COOCH₃ 370.0473 3 6-Cl —CF₃ —C≡C-cycPr —CH₃ 328.0706 4 6-Cl —CF₃ —C≡C-cycPr —CH₂CH≡CH₂ 354.0861 5 6-Cl —CF₃ —C≡C-cycPr —CH₂Ph 402.0846 6 6-Cl —CF₃ —C≡C-cycPr —CH(CH₃) 356.1016 7 5,6-diF —CF₃ —C≡C-cycPr —H 316.0739 8 6-Cl —CF₃ —C≡C-cycPr —OH 330.0495 * Unless otherwise indicated, stereochemisty is (+/−).

Tables 2 and 3 show representative compounds envisaged by the scope of the present invention. Each formula shown at the start of Table 2 and Table 3 is intended to be paired with each entry in the table which follows. Unless otherwise noted, the compounds represented in Table 2 and Table 3 have stereochemistry (+/−) and, in R², all double bonds are trans.

TABLE 2

Ex # G R¹ R² 1001 5-Cl CF₃ CH₂CH₂CH₃ 1002 5-Cl CF₃ CH₂CH₂CH₂CH₃ 1003 5-Cl CF₃ CH₂CH₂CH₂CH₂CH₃ 1004 5-Cl CF₃ CH₂CH₂CH(CH₃)₂ 1005 5-Cl CF₃ CH₂CH₂-tBu 1006 5-Cl CF₃ CH₂-cycPr 1007 5-Cl CF₃ CH₂—Ph 1008 5-Cl CF₃ CH₂-2-Pyridyl 1009 5-Cl CF₃ CH₂-3-Pyridyl 1010 5-Cl CF₃ CH₂-4-Pyridyl 1011 5-Cl CF₃ CH₂-2-furanyl 1012 5-Cl CF₃ CH₂-3-furanyl 1013 5-Cl CF₃ CH₂-2-thienyl 1014 5-Cl CF₃ CH₂-3-thienyl 1015 5-Cl CF₃ CH₂CH₂-cycPr 1016 5-Cl CF₃ CH₂CH₂—Ph 1017 5-Cl CF₃ CH₂CH₂-2-Pyridyl 1018 5-Cl CF₃ CH₂CH₂-3-Pyridyl 1019 5-Cl CF₃ CH₂CH₂-4-Pyridyl 1020 5-Cl CF₃ CH₂CH₂-2-furanyl 1021 5-Cl CF₃ CH₂CH₂-3-furanyl 1022 5-Cl CF₃ CH₂CH₂-2-thienyl 1023 5-Cl CF₃ CH₂CH₂-3-thienyl 1024 5-Cl CF₃ C≡C—Et 1025 5-Cl CF₃ C≡C-iPr 1026 5-Cl CF₃ C≡C-cycPr 1027 5-Cl CF₃ C≡C-1-(Me)cycPr 1028 5-Cl CF₃ C≡C-2-pyridyl 1029 5-Cl CF₃ C≡C-3-pyridyl 1030 5-Cl CF₃ C≡C-4-pyridyl 1031 5-Cl CF₃ C≡C-2-furanyl 1032 5-Cl CF₃ C≡C-3-furanyl 1033 5-Cl CF₃ C≡C-2-thienyl 1034 5-Cl CF₃ C≡C-3-thienyl 1035 5-Cl CF₃ CH═CH—Et 1036 5-Cl CF₃ CH═CH-iPr 1037 5-Cl CF₃ CH═CH-cycPr 1038 5-Cl CF₃ CH═CH-1-(Me)cycPr 1039 5-Cl CF₃ CH═CH-2-pyridyl 1040 5-Cl CF₃ CH═CH-3-pyridyl 1041 5-Cl CF₃ CH═CH-4-pyridyl 1042 5-Cl CF₃ CH═CH-2-furanyl 1043 5-Cl CF₃ CH═CH-3-furanyl 1044 5-Cl CF₃ CH═CH-2-thienyl 1045 5-Cl CF₃ CH═CH-3-thienyl 1046 5-Cl CF₃ CH₂—C≡C-cycPr 1047 5-Cl CF₃ CH₂—C≡C-2-furanyl 1048 5-Cl CF₃ CH₂CH═CH-cycPr 1049 5-Cl CF₃ CH₂CH═CH-2-furanyl 1050 5-Cl CF₃ CH═CHCH₂-cycPr 1051 5-Cl CF₃ CH═CHCH₂-2-furanyl 1052 6-Cl CF₃ CH₂CH₂CH₃ 1053 6-Cl CF₃ CH₂CH₂CH₂CH₃ 1054 6-Cl CF₃ CH₂CH₂CH₂CH₂CH₃ 1055 6-Cl CF₃ CH₂CH₂CH(CH₃)₂ 1056 6-Cl CF₃ CH₂CH₂-tBu 1057 6-Cl CF₃ CH₂-cycPr 1058 6-Cl CF₃ CH₂—Ph 1059 6-Cl CF₃ CH₂-2-Pyridyl 1060 6-Cl CF₃ CH₂-3-Pyridyl 1061 6-Cl CF₃ CH₂-4-Pyridyl 1062 6-Cl CF₃ CH₂-2-furanyl 1063 6-Cl CF₃ CH₂-3-furanyl 1064 6-Cl CF₃ CH₂-2-thienyl 1065 6-Cl CF₃ CH₂-3-thienyl 1066 6-Cl CF₃ CH₂CH₂-cycPr 1067 6-Cl CF₃ CH₂CH₂—Ph 1068 6-Cl CF₃ CH₂CH₂-2-Pyridyl 1069 6-Cl CF₃ CH₂CH₂-3-Pyridyl 1070 6-Cl CF₃ CH₂CH₂-4-Pyridyl 1071 6-Cl CF₃ CH₂CH₂-2-furanyl 1072 6-Cl CF₃ CH₂CH₂-3-furanyl 1073 6-Cl CF₃ CH₂CH₂-2-thienyl 1074 6-Cl CF₃ CH₂CH₂-3-thienyl 1075 6-Cl CF₃ C≡C—Et 1076 6-Cl CF₃ C≡C-iPr 1077 6-Cl CF₃ C≡C-cycPr 1078 6-Cl CF₃ C≡C-1-(Me)cycPr 1079 6-Cl CF₃ C≡C-2-pyridyl 1080 6-Cl CF₃ C≡C-3-pyridyl 1081 6-Cl CF₃ C≡C-4-pyridyl 1082 6-Cl CF₃ C≡C-2-furanyl 1083 6-Cl CF₃ C≡C-3-furanyl 1084 6-Cl CF₃ C≡C-2-thienyl 1085 6-Cl CF₃ C≡C-3-thienyl 1086 6-Cl CF₃ CH═CH—Et 1087 6-Cl CF₃ CH═CH-iPr 1088 6-Cl CF₃ CH═CH-cycPr 1089 6-Cl CF₃ CH═CH-1-(Me)cycPr 1090 6-Cl CF₃ CH═CH-2-pyridyl 1091 6-Cl CF₃ CH═CH-3-pyridyl 1092 6-Cl CF₃ CH═CH-4-pyridyl 1093 6-Cl CF₃ CH═CH-2-furanyl 1094 6-Cl CF₃ CH═CH-3-furanyl 1095 6-Cl CF₃ CH═CH-2-thienyl 1096 6-Cl CF₃ CH═CH-3-thienyl 1097 6-Cl CF₃ CH₂—C≡C-cycPr 1098 6-Cl CF₃ CH₂—C≡C-2-furanyl 1099 6-Cl CF₃ CH₂CH═CH-cycPr 1100 6-Cl CF₃ CH₂CH═CH-2-furanyl 1101 6-Cl CF₃ CH═CHCH₂-cycPr 1102 6-Cl CF₃ CH═CHCH₂-2-furanyl 1103 5-F CF₃ CH₂CH₂CH₃ 1104 5-F CF₃ CH₂CH₂CH₂CH₃ 1105 5-F CF₃ CH₂CH₂CH₂CH₂CH₃ 1106 5-F CF₃ CH₂CH₂CH(CH₃)₂ 1107 5-F CF₃ CH₂CH₂-tBu 1108 5-F CF₃ CH₂-cycPr 1109 5-F CF₃ CH₂—Ph 1110 5-F CF₃ CH₂-2-Pyridyl 1111 5-F CF₃ CH₂-3-Pyridyl 1112 5-F CF₃ CH₂-4-Pyridyl 1113 5-F CF₃ CH₂-2-furanyl 1114 5-F CF₃ CH₂-3-furanyl 1115 5-F CF₃ CH₂-2-thienyl 1116 5-F CF₃ CH₂-3-thienyl 1117 5-F CF₃ CH₂CH₂-cycPr 1118 5-F CF₃ CH₂CH₂—Ph 1119 5-F CF₃ CH₂CH₂-2-Pyridyl 1120 5-F CF₃ CH₂CH₂-3-Pyridyl 1121 5-F CF₃ CH₂CH₂-4-Pyridyl 1122 5-F CF₃ CH₂CH₂-2-furanyl 1123 5-F CF₃ CH₂CH₂-3-furanyl 1124 5-F CF₃ CH₂CH₂-2-thienyl 1125 5-F CF₃ CH₂CH₂-3-thienyl 1126 5-F CF₃ C≡C—Et 1127 5-F CF₃ C≡C-iPr 1128 5-F CF₃ C≡C-cycPr 1129 5-F CF₃ C≡C-1-(Me)cycPr 1130 5-F CF₃ C≡C-2-pyridyl 1131 5-F CF₃ C≡C-3-pyridyl 1132 5-F CF₃ C≡C-4-pyridyl 1133 5-F CF₃ C≡C-2-furanyl 1134 5-F CF₃ C≡C-3-furanyl 1135 5-F CF₃ C≡C-2-thienyl 1136 5-F CF₃ C≡C-3-thienyl 1137 5-F CF₃ CH═CH—Et 1138 5-F CF₃ CH═CH-iPr 1139 5-F CF₃ CH═CH-cycPr 1140 5-F CF₃ CH═CH-1-(Me)cycPr 1141 5-F CF₃ CH═CH-2-pyridyl 1142 5-F CF₃ CH═CH-3-pyridyl 1143 5-F CF₃ CH═CH-4-pyridyl 1144 5-F CF₃ CH═CH-2-furanyl 1145 5-F CF₃ CH═CH-3-furanyl 1146 5-F CF₃ CH═CH-2-thienyl 1147 5-F CF₃ CH═CH-3-thienyl 1148 5-F CF₃ CH₂—C≡C-cycPr 1149 5-F CF₃ CH₂—C≡C-2-furanyl 1150 5-F CF₃ CH₂CH═CH-cycPr 1151 5-F CF₃ CH₂CH═CH-2-furanyl 1152 5-F CF₃ CH═CHCH₂-cycPr 1153 5-F CF₃ CH═CHCH₂-2-furanyl 1154 6-F CF₃ CH₂CH₂CH₃ 1155 6-F CF₃ CH₂CH₂CH₂CH₃ 1156 6-F CF₃ CH₂CH₂CH₂CH₂CH₃ 1157 6-F CF₃ CH₂CH₂CH(CH₃)₂ 1158 6-F CF₃ CH₂CH₂-tBu 1159 6-F CF₃ CH₂-cycPr 1160 6-F CF₃ CH₂—Ph 1161 6-F CF₃ CH₂-2-Pyridyl 1162 6-F CF₃ CH₂-3-Pyridyl 1163 6-F CF₃ CH₂-4-Pyridyl 1164 6-F CF₃ CH₂-2-furanyl 1165 6-F CF₃ CH₂-3-furanyl 1166 6-F CF₃ CH₂-2-thienyl 1167 6-F CF₃ CH₂-3-thienyl 1168 6-F CF₃ CH₂CH₂-cycPr 1169 6-F CF₃ CH₂CH₂—Ph 1170 6-F CF₃ CH₂CH₂-2-Pyridyl 1171 6-F CF₃ CH₂CH₂-3-Pyridyl 1172 6-F CF₃ CH₂CH₂-4-Pyridyl 1173 6-F CF₃ CH₂CH₂-2-furanyl 1174 6-F CF₃ CH₂CH₂-3-furanyl 1175 6-F CF₃ CH₂CH₂-2-thienyl 1176 6-F CF₃ CH₂CH₂-3-thienyl 1177 6-F CF₃ C≡C—Et 1178 6-F CF₃ C≡C-iPr 1179 6-F CF₃ C≡C-cycPr 1180 6-F CF₃ C≡C-1-(Me)cycPr 1181 6-F CF₃ C≡C-2-pyridyl 1182 6-F CF₃ C≡C-3-pyridyl 1183 6-F CF₃ C≡C-4-pyridyl 1184 6-F CF₃ C≡C-2-furanyl 1185 6-F CF₃ C≡C-3-furanyl 1186 6-F CF₃ C≡C-2-thienyl 1187 6-F CF₃ C≡C-3-thienyl 1188 6-F CF₃ CH═CH—Et 1189 6-F CF₃ CH═CH-iPr 1190 6-F CF₃ CH═CH-cycPr 1191 6-F CF₃ CH═CH-1-(Me)cycPr 1192 6-F CF₃ CH═CH-2-pyridyl 1193 6-F CF₃ CH═CH-3-pyridyl 1194 6-F CF₃ CH═CH-4-pyridyl 1195 6-F CF₃ CH═CH-2-furanyl 1196 6-F CF₃ CH═CH-3-furanyl 1197 6-F CF₃ CH═CH-2-thienyl 1198 6-F CF₃ CH═CH-3-thienyl 1199 6-F CF₃ CH₂—C≡C-cycPr 1200 6-F CF₃ CH₂—C≡C-2-furanyl 1201 6-F CF₃ CH₂CH═CH-cycPr 1202 6-F CF₃ CH₂CH═CH-2-furanyl 1203 6-F CF₃ CH═CHCH₂-cycPr 1204 6-F CF₃ CH═CHCH₂-2-furanyl 1205 5,6-diCl CF₃ CH₂CH₂CH₃ 1206 5,6-diCl CF₃ CH₂CH₂CH₂CH₃ 1207 5,6-diCl CF₃ CH₂CH₂CH₂CH₂CH₃ 1208 5,6-diCl CF₃ CH₂CH₂CH(CH₃)₂ 1209 5,6-diCl CF₃ CH₂CH₂-tBu 1210 5,6-diCl CF₃ CH₂-cycPr 1211 5,6-diCl CF₃ CH₂—Ph 1212 5,6-diCl CF₃ CH₂-2-Pyridyl 1213 5,6-diCl CF₃ CH₂-3-Pyridyl 1214 5,6-diCl CF₃ CH₂-4-Pyridyl 1215 5,6-diCl CF₃ CH₂-2-furanyl 1216 5,6-diCl CF₃ CH₂-3-furanyl 1217 5,6-diCl CF₃ CH₂-2-thienyl 1218 5,6-diCl CF₃ CH₂-3-thienyl 1219 5,6-diCl CF₃ CH₂CH₂-cycPr 1220 5,6-diCl CF₃ CH₂CH₂—Ph 1221 5,6-diCl CF₃ CH₂CH₂-2-Pyridyl 1222 5,6-diCl CF₃ CH₂CH₂-3-Pyridyl 1223 5,6-diCl CF₃ CH₂CH₂-4-Pyridyl 1224 5,6-diCl CF₃ CH₂CH₂-2-furanyl 1225 5,6-diCl CF₃ CH₂CH₂-3-furanyl 1226 5,6-diCl CF₃ CH₂CH₂-2-thienyl 1227 5,6-diCl CF₃ CH₂CH₂-3-thienyl 1228 5,6-diCl CF₃ C≡C—Et 1229 5,6-diCl CF₃ C≡C-iPr 1230 5,6-diCl CF₃ C≡C-cycPr 1231 5,6-diCl CF₃ C≡C-1-(Me)cycPr 1232 5,6-diCl CF₃ C≡C-2-pyridyl 1233 5,6-diCl CF₃ C≡C-3-pyridyl 1234 5,6-diCl CF₃ C≡C-4-pyridyl 1235 5,6-diCl CF₃ C≡C-2-furanyl 1236 5,6-diCl CF₃ C≡C-3-furanyl 1237 5,6-diCl CF₃ C≡C-2-thienyl 1238 5,6-diCl CF₃ C≡C-3-thienyl 1239 5,6-diCl CF₃ CH═CH—Et 1240 5,6-diCl CF₃ CH═CH-iPr 1241 5,6-diCl CF₃ CH═CH-cycPr 1242 5,6-diCl CF₃ CH═CH-1-(Me)cycPr 1243 5,6-diCl CF₃ CH═CH-2-pyridyl 1244 5,6-diCl CF₃ CH═CH-3-pyridyl 1245 5,6-diCl CF₃ CH═CH-4-pyridyl 1246 5,6-diCl CF₃ CH═CH-2-furanyl 1247 5,6-diCl CF₃ CH═CH-3-furanyl 1248 5,6-diCl CF₃ CH═CH-2-thienyl 1249 5,6-diCl CF₃ CH═CH-3-thienyl 1250 5,6-diCl CF₃ CH₂—C≡C-cycPr 1251 5,6-diCl CF₃ CH₂—C≡C-2-furanyl 1252 5,6-diCl CF₃ CH₂CH═CH-cycPr 1253 5,6-diCl CF₃ CH₂CH═CH-2-furanyl 1254 5,6-diCl CF₃ CH═CHCH₂-cycPr 1255 5,6-diCl CF₃ CH═CHCH₂-2-furanyl 1256 5,6-diF CF₃ CH₂CH₂CH₃ 1257 5,6-diF CF₃ CH₂CH₂CH₂CH₃ 1258 5,6-diF CF₃ CH₂CH₂CH₂CH₂CH₃ 1259 5,6-diF CF₃ CH₂CH₂CH(CH₃)₂ 1260 5,6-diF CF₃ CH₂CH₂-tBu 1261 5,6-diF CF₃ CH₂-cycPr 1262 5,6-diF CF₃ CH₂—Ph 1263 5,6-diF CF₃ CH₂-2-Pyridyl 1264 5,6-diF CF₃ CH₂-3-Pyridyl 1265 5,6-diF CF₃ CH₂-4-Pyridyl 1266 5,6-diF CF₃ CH₂-2-furanyl 1267 5,6-diF CF₃ CH₂-3-furanyl 1268 5,6-diF CF₃ CH₂-2-thienyl 1269 5,6-diF CF₃ CH₂-3-thienyl 1270 5,6-diF CF₃ CH₂CH₂-cycPr 1271 5,6-diF CF₃ CH₂CH₂—Ph 1272 5,6-diF CF₃ CH₂CH₂-2-Pyridyl 1273 5,6-diF CF₃ CH₂CH₂-3-Pyridyl 1274 5,6-diF CF₃ CH₂CH₂-4-Pyridyl 1275 5,6-diF CF₃ CH₂CH₂-2-furanyl 1276 5,6-diF CF₃ CH₂CH₂-3-furanyl 1277 5,6-diF CF₃ CH₂CH₂-2-thienyl 1278 5,6-diF CF₃ CH₂CH₂-3-thienyl 1279 5,6-diF CF₃ C≡C—Et 1280 5,6-diF CF₃ C≡C-iPr 1281 5,6-diF CF₃ C≡C-cycPr 1282 5,6-diF CF₃ C≡C-1-(Me)cycPr 1283 5,6-diF CF₃ C≡C-2-pyridyl 1284 5,6-diF CF₃ C≡C-3-pyridyl 1285 5,6-diF CF₃ C≡C-4-pyridyl 1286 5,6-diF CF₃ C≡C-2-furanyl 1287 5,6-diF CF₃ C≡C-3-furanyl 1288 5,6-diF CF₃ C≡C-2-thienyl 1289 5,6-diF CF₃ C≡C-3-thienyl 1290 5,6-diF CF₃ CH═CH—Et 1291 5,6-diF CF₃ CH═CH-iPr 1292 5,6-diF CF₃ CH═CH-cycPr 1293 5,6-diF CF₃ CH═CH-1-(Me)cycPr 1294 5,6-diF CF₃ CH═CH-2-pyridyl 1295 5,6-diF CF₃ CH═CH-3-pyridyl 1296 5,6-diF CF₃ CH═CH-4-pyridyl 1297 5,6-diF CF₃ CH═CH-2-furanyl 1298 5,6-diF CF₃ CH═CH-3-furanyl 1299 5,6-diF CF₃ CH═CH-2-thienyl 1300 5,6-diF CF₃ CH═CH-3-thienyl 1301 5,6-diF CF₃ CH₂—C≡C-cycPr 1302 5,6-diF CF₃ CH₂—C≡C-2-furanyl 1303 5,6-diF CF₃ CH₂CH═CH-cycPr 1304 5,6-diF CF₃ CH₂CH═CH-2-furanyl 1305 5,6-diF CF₃ CH═CHCH₂-cycPr 1306 5,6-diF CF₃ CH═CHCH₂-2-furanyl 1307 5-Cl, 6-F CF₃ CH₂CH₂CH₃ 1308 5-Cl, 6-F CF₃ CH₂CH₂CH₂CH₃ 1309 5-Cl, 6-F CF₃ CH₂CH₂CH₂CH₂CH₃ 1310 5-Cl, 6-F CF₃ CH₂CH₂CH(CH₃)₂ 1311 5-Cl, 6-F CF₃ CH₂CH₂-tBu 1312 5-Cl, 6-F CF₃ CH₂-cycPr 1313 5-Cl, 6-F CF₃ CH₂—Ph 1314 5-Cl, 6-F CF₃ CH₂-2-Pyridyl 1315 5-Cl, 6-F CF₃ CH₂-3-Pyridyl 1316 5-Cl, 6-F CF₃ CH₂-4-Pyridyl 1317 5-Cl, 6-F CF₃ CH₂-2-furanyl 1318 5-Cl, 6-F CF₃ CH₂-3-furanyl 1319 5-Cl, 6-F CF₃ CH₂-2-thienyl 1320 5-Cl, 6-F CF₃ CH₂-3-thienyl 1321 5-Cl, 6-F CF₃ CH₂CH₂-cycPr 1322 5-Cl, 6-F CF₃ CH₂CH₂—Ph 1323 5-Cl, 6-F CF₃ CH₂CH₂-2-Pyridyl 1324 5-Cl, 6-F CF₃ CH₂CH₂-3-Pyridyl 1325 5-Cl, 6-F CF₃ CH₂CH₂-4-Pyridyl 1326 5-Cl, 6-F CF₃ CH₂CH₂-2-furanyl 1327 5-Cl, 6-F CF₃ CH₂CH₂-3-furanyl 1328 5-Cl, 6-F CF₃ CH₂CH₂-2-thienyl 1329 5-Cl, 6-F CF₃ CH₂CH₂-3-thienyl 1330 5-Cl, 6-F CF₃ C≡C—Et 1331 5-Cl, 6-F CF₃ C≡C-iPr 1332 5-Cl, 6-F CF₃ C≡C-cycPr 1333 5-Cl, 6-F CF₃ C≡C-1-(Me)cycPr 1334 5-Cl, 6-F CF₃ C≡C-2-pyridyl 1335 5-Cl, 6-F CF₃ C≡C-3-pyridyl 1336 5-Cl, 6-F CF₃ C≡C-4-pyridyl 1337 5-Cl, 6-F CF₃ C≡C-2-furanyl 1338 5-Cl, 6-F CF₃ C≡C-3-furanyl 1339 5-Cl, 6-F CF₃ C≡C-2-thienyl 1340 5-Cl, 6-F CF₃ C≡C-3-thienyl 1341 5-Cl, 6-F CF₃ CH═CH—Et 1342 5-Cl, 6-F CF₃ CH═CH-iPr 1343 5-Cl, 6-F CF₃ CH═CH-cycPr 1344 5-Cl, 6-F CF₃ CH═CH-1-(Me)cycPr 1345 5-Cl, 6-F CF₃ CH═CH-2-pyridyl 1346 5-Cl, 6-F CF₃ CH═CH-3-pyridyl 1347 5-Cl, 6-F CF₃ CH═CH-4-pyridyl 1348 5-Cl, 6-F CF₃ CH═CH-2-furanyl 1349 5-Cl, 6-F CF₃ CH═CH-3-furanyl 1350 5-Cl, 6-F CF₃ CH═CH-2-thienyl 1351 5-Cl, 6-F CF₃ CH═CH-3-thienyl 1352 5-Cl, 6-F CF₃ CH₂—C≡C-cycPr 1353 5-Cl, 6-F CF₃ CH₂—C≡C-2-furanyl 1354 5-Cl, 6-F CF₃ CH₂CH═CH-cycPr 1355 5-Cl, 6-F CF₃ CH₂CH═CH-2-furanyl 1356 5-Cl, 6-F CF₃ CH═CHCH₂-cycPr 1357 5-Cl, 6-F CF₃ CH═CHCH₂-2-furanyl 1358 5-F, 6-Cl CF₃ CH₂CH₂CH₃ 1359 5-F, 6-Cl CF₃ CH₂CH₂CH₂CH₃ 1360 5-F, 6-Cl CF₃ CH₂CH₂CH₂CH₂CH₃ 1361 5-F, 6-Cl CF₃ CH₂CH₂CH(CH₃)₂ 1362 5-F, 6-Cl CF₃ CH₂CH₂-tBu 1363 5-F, 6-Cl CF₃ CH₂-cycPr 1364 5-F, 6-Cl CF₃ CH₂—Ph 1365 5-F, 6-Cl CF₃ CH₂-2-Pyridyl 1366 5-F, 6-Cl CF₃ CH₂-3-Pyridyl 1367 5-F, 6-Cl CF₃ CH₂-4-Pyridyl 1368 5-F, 6-Cl CF₃ CH₂-2-furanyl 1369 5-F, 6-Cl CF₃ CH₂-3-furanyl 1370 5-F, 6-Cl CF₃ CH₂-2-thienyl 1371 5-F, 6-Cl CF₃ CH₂-3-thienyl 1372 5-F, 6-Cl CF₃ CH₂CH₂-cycPr 1373 5-F, 6-Cl CF₃ CH₂CH₂—Ph 1374 5-F, 6-Cl CF₃ CH₂CH₂-2-Pyridyl 1375 5-F, 6-Cl CF₃ CH₂CH₂-3-Pyridyl 1376 5-F, 6-Cl CF₃ CH₂CH₂-4-Pyridyl 1377 5-F, 6-Cl CF₃ CH₂CH₂-2-furanyl 1378 5-F, 6-Cl CF₃ CH₂CH₂-3-furanyl 1379 5-F, 6-Cl CF₃ CH₂CH₂-2-thienyl 1380 5-F, 6-Cl CF₃ CH₂CH₂-3-thienyl 1381 5-F, 6-Cl CF₃ C≡C—Et 1382 5-F, 6-Cl CF₃ C≡C-iPr 1383 5-F, 6-Cl CF₃ C≡C-cycPr 1384 5-F, 6-Cl CF₃ C≡C-1-(Me)cycPr 1385 5-F, 6-Cl CF₃ C≡C-2-pyridyl 1386 5-F, 6-Cl CF₃ C≡C-3-pyridyl 1387 5-F, 6-Cl CF₃ C≡C-4-pyridyl 1388 5-F, 6-Cl CF₃ C≡C-2-furanyl 1389 5-F, 6-Cl CF₃ C≡C-3-furanyl 1390 5-F, 6-Cl CF₃ C≡C-2-thienyl 1391 5-F, 6-Cl CF₃ C≡C-3-thienyl 1392 5-F, 6-Cl CF₃ CH═CH—Et 1393 5-F, 6-Cl CF₃ CH═CH-iPr 1394 5-F, 6-Cl CF₃ CH═CH-cycPr 1395 5-F, 6-Cl CF₃ CH═CH-1-(Me)cycPr 1396 5-F, 6-Cl CF₃ CH═CH-2-pyridyl 1397 5-F, 6-Cl CF₃ CH═CH-3-pyridyl 1398 5-F, 6-Cl CF₃ CH═CH-4-pyridyl 1399 5-F, 6-Cl CF₃ CH═CH-2-furanyl 1400 5-F, 6-Cl CF₃ CH═CH-3-furanyl 1401 5-F, 6-Cl CF₃ CH═CH-2-thienyl 1402 5-F, 6-Cl CF₃ CH═CH-3-thienyl 1403 5-F, 6-Cl CF₃ CH₂—C≡C-cycPr 1404 5-F, 6-Cl CF₃ CH₂—C≡C-2-furanyl 1405 5-F, 6-Cl CF₃ CH₂CH═CH-cycPr 1406 5-F, 6-Cl CF₃ CH₂CH═CH-2-furanyl 1407 5-F, 6-Cl CF₃ CH═CHCH₂-cycPr 1408 5-F, 6-Cl CF₃ CH═CHCH₂-2-furanyl 1409 6-CH₃ CF₃ CH₂CH₂CH₃ 1410 6-CH₃ CF₃ CH₂CH₂CH₂CH₃ 1411 6-CH₃ CF₃ CH₂CH₂CH₂CH₂CH₃ 1412 6-CH₃ CF₃ CH₂CH₂CH(CH₃)₂ 1413 6-CH₃ CF₃ CH₂CH₂-tBu 1414 6-CH₃ CF₃ CH₂-cycPr 1415 6-CH₃ CF₃ CH₂—Ph 1416 6-CH₃ CF₃ CH₂-2-Pyridyl 1417 6-CH₃ CF₃ CH₂-3-Pyridyl 1418 6-CH₃ CF₃ CH₂-4-Pyridyl 1419 6-CH₃ CF₃ CH₂-2-furanyl 1420 6-CH₃ CF₃ CH₂-3-furanyl 1421 6-CH₃ CF₃ CH₂-2-thienyl 1422 6-CH₃ CF₃ CH₂-3-thienyl 1423 6-CH₃ CF₃ CH₂CH₂-cycPr 1424 6-CH₃ CF₃ CH₂CH₂—Ph 1425 6-CH₃ CF₃ CH₂CH₂-2-Pyridyl 1426 6-CH₃ CF₃ CH₂CH₂-3-Pyridyl 1427 6-CH₃ CF₃ CH₂CH₂-4-Pyridyl 1428 6-CH₃ CF₃ CH₂CH₂-2-furanyl 1429 6-CH₃ CF₃ CH₂CH₂-3-furanyl 1430 6-CH₃ CF₃ CH₂CH₂-2-thienyl 1431 6-CH₃ CF₃ CH₂CH₂-3-thienyl 1432 6-CH₃ CF₃ C≡C—Et 1433 6-CH₃ CF₃ C≡C-iPr 1434 6-CH₃ CF₃ C≡C-cycPr 1435 6-CH₃ CF₃ C≡C-1-(Me)cycPr 1436 6-CH₃ CF₃ C≡C-2-pyridyl 1437 6-CH₃ CF₃ C≡C-3-pyridyl 1438 6-CH₃ CF₃ C≡C-4-pyridyl 1439 6-CH₃ CF₃ C≡C-2-furanyl 1440 6-CH₃ CF₃ C≡C-3-furanyl 1441 6-CH₃ CF₃ C≡C-2-thienyl 1442 6-CH₃ CF₃ C≡C-3-thienyl 1443 6-CH₃ CF₃ CH═CH—Et 1444 6-CH₃ CF₃ CH═CH-iPr 1445 6-CH₃ CF₃ CH═CH-cycPr 1446 6-CH₃ CF₃ CH═CH-1-(Me)cycPr 1447 6-CH₃ CF₃ CH═CH-2-pyridyl 1448 6-CH₃ CF₃ CH═CH-3-pyridyl 1449 6-CH₃ CF₃ CH═CH-4-pyridyl 1450 6-CH₃ CF₃ CH═CH-2-furanyl 1451 6-CH₃ CF₃ CH═CH-3-furanyl 1452 6-CH₃ CF₃ CH═CH-2-thienyl 1453 6-CH₃ CF₃ CH═CH-3-thienyl 1454 6-CH₃ CF₃ CH₂—C≡C-cycPr 1455 6-CH₃ CF₃ CH₂—C≡C-2-furanyl 1456 6-CH₃ CF₃ CH₂CH═CH-cycPr 1457 6-CH₃ CF₃ CH₂CH═CH-2-furanyl 1458 6-CH₃ CF₃ CH═CHCH₂-cycPr 1459 6-CH₃ CF₃ CH═CHCH₂-2-furanyl 1460 6-OCH₃ CF₃ CH₂CH₂CH₃ 1461 6-OCH₃ CF₃ CH₂CH₂CH₂CH₃ 1462 6-OCH₃ CF₃ CH₂CH₂CH₂CH₂CH₃ 1463 6-OCH₃ CF₃ CH₂CH₂CH(CH₃)₂ 1464 6-OCH₃ CF₃ CH₂CH₂-tBu 1465 6-OCH₃ CF₃ CH₂-cycPr 1466 6-OCH₃ CF₃ CH₂—Ph 1467 6-OCH₃ CF₃ CH₂-2-Pyridyl 1478 6-OCH₃ CF₃ CH₂-3-Pyridyl 1479 6-OCH₃ CF₃ CH₂-4-Pyridyl 1470 6-OCH₃ CF₃ CH₂-2-furanyl 1471 6-OCH₃ CF₃ CH₂-3-furanyl 1472 6-OCH₃ CF₃ CH₂-2-thienyl 1473 6-OCH₃ CF₃ CH₂-3-thienyl 1474 6-OCH₃ CF₃ CH₂CH₂-cycPr 1475 6-OCH₃ CF₃ CH₂CH₂—Ph 1476 6-OCH₃ CF₃ CH₂CH₂-2-Pyridyl 1477 6-OCH₃ CF₃ CH₂CH₂-3-Pyridyl 1488 6-OCH₃ CF₃ CH₂CH₂-4-Pyridyl 1489 6-OCH₃ CF₃ CH₂CH₂-2-furanyl 1480 6-OCH₃ CF₃ CH₂CH₂-3-furanyl 1481 6-OCH₃ CF₃ CH₂CH₂-2-thienyl 1482 6-OCH₃ CF₃ CH₂CH₂-3-thienyl 1483 6-OCH₃ CF₃ C≡C—Et 1484 6-OCH₃ CF₃ C≡C-iPr 1485 6-OCH₃ CF₃ C≡C-cycPr 1486 6-OCH₃ CF₃ C≡C-1-(Me)cycPr 1487 6-OCH₃ CF₃ C≡C-2-pyridyl 1488 6-OCH₃ CF₃ C≡C-3-pyridyl 1489 6-OCH₃ CF₃ C≡C-4-pyridyl 1490 6-OCH₃ CF₃ C≡C-2-furanyl 1491 6-OCH₃ CF₃ C≡C-3-furanyl 1492 6-OCH₃ CF₃ C≡C-2-thienyl 1493 6-OCH₃ CF₃ C≡C-3-thienyl 1494 6-OCH₃ CF₃ CH═CH—Et 1495 6-OCH₃ CF₃ CH═CH-iPr 1496 6-OCH₃ CF₃ CH═CH-cycPr 1497 6-OCH₃ CF₃ CH═CH-1-(Me)cycPr 1498 6-OCH₃ CF₃ CH═CH-2-pyridyl 1499 6-OCH₃ CF₃ CH═CH-3-pyridyl 1500 6-OCH₃ CF₃ CH═CH-4-pyridyl 1501 6-OCH₃ CF₃ CH═CH-2-furanyl 1502 6-OCH₃ CF₃ CH═CH-3-furanyl 1503 6-OCH₃ CF₃ CH═CH-2-thienyl 1504 6-OCH₃ CF₃ CH═CH-3-thienyl 1505 6-OCH₃ CF₃ CH₂—C≡C-cycPr 1506 6-OCH₃ CF₃ CH₂—C≡C-2-furanyl 1507 6-OCH₃ CF₃ CH₂CH═CH-cycPr 1508 6-OCH₃ CF₃ CH₂CH═CH-2-furanyl 1509 6-OCH₃ CF₃ CH═CHCH₂-cycPr 1510 6-OCH₃ CF₃ CH═CHCH₂-2-furanyl 1511 5,6-OCH₂O— CF₃ CH₂CH₂CH₃ 1512 5,6-OCH₂O— CF₃ CH₂CH₂CH₂CH₃ 1513 5,6-OCH₂O— CF₃ CH₂CH₂CH₂CH₂CH₃ 1514 5,6-OCH₂O— CF₃ CH₂CH₂CH(CH₃)₂ 1515 5,6-OCH₂O— CF₃ CH₂CH₂-tBu 1516 5,6-OCH₂O— CF₃ CH₂-cycPr 1517 5,6-OCH₂O— CF₃ CH₂—Ph 1518 5,6-OCH₂O— CF₃ CH₂-2-Pyridyl 1519 5,6-OCH₂O— CF₃ CH₂-3-Pyridyl 1520 5,6-OCH₂O— CF₃ CH₂-4-Pyridyl 1521 5,6-OCH₂O— CF₃ CH₂-2-furanyl 1522 5,6-OCH₂O— CF₃ CH₂-3-furanyl 1523 5,6-OCH₂O— CF₃ CH₂-2-thienyl 1524 5,6-OCH₂O— CF₃ CH₂-3-thienyl 1525 5,6-OCH₂O— CF₃ CH₂CH₂-cycPr 1526 5,6-OCH₂O— CF₃ CH₂CH₂—Ph 1527 5,6-OCH₂O— CF₃ CH₂CH₂-2-Pyridyl 1528 5,6-OCH₂O— CF₃ CH₂CH₂-3-Pyridyl 1529 5,6-OCH₂O— CF₃ CH₂CH₂-4-Pyridyl 1530 5,6-OCH₂O— CF₃ CH₂CH₂-2-furanyl 1531 5,6-OCH₂O— CF₃ CH₂CH₂-3-furanyl 1532 5,6-OCH₂O— CF₃ CH₂CH₂-2-thienyl 1533 5,6-OCH₂O— CF₃ CH₂CH₂-3-thienyl 1534 5,6-OCH₂O— CF₃ C≡C—Et 1535 5,6-OCH₂O— CF₃ C≡C-iPr 1536 5,6-OCH₂O— CF₃ C≡C-cycPr 1537 5,6-OCH₂O— CF₃ C≡C-1-(Me)cycPr 1538 5,6-OCH₂O— CF₃ C≡C-2-pyridyl 1539 5,6-OCH₂O— CF₃ C≡C-3-pyridyl 1540 5,6-OCH₂O— CF₃ C≡C-4-pyridyl 1541 5,6-OCH₂O— CF₃ C≡C-2-furanyl 1542 5,6-OCH₂O— CF₃ C≡C-3-furanyl 1543 5,6-OCH₂O— CF₃ C≡C-2-thienyl 1544 5,6-OCH₂O— CF₃ C≡C-3-thienyl 1545 5,6-OCH₂O— CF₃ CH═CH—Et 1546 5,6-OCH₂O— CF₃ CH═CH-iPr 1547 5,6-OCH₂O— CF₃ CH═CH-cycPr 1548 5,6-OCH₂O— CF₃ CH═CH-1-(Me)cycPr 1549 5,6-OCH₂O— CF₃ CH═CH-2-pyridyl 1550 5,6-OCH₂O— CF₃ CH═CH-3-pyridyl 1551 5,6-OCH₂O— CF₃ CH═CH-4-pyridyl 1552 5,6-OCH₂O— CF₃ CH═CH-2-furanyl 1553 5,6-OCH₂O— CF₃ CH═CH-3-furanyl 1554 5,6-OCH₂O— CF₃ CH═CH-2-thienyl 1555 5,6-OCH₂O— CF₃ CH═CH-3-thienyl 1556 5,6-OCH₂O— CF₃ CH₂—C≡C-cycPr 1557 5,6-OCH₂O— CF₃ CH₂—C≡C-2-furanyl 1558 5,6-OCH₂O— CF₃ CH₂CH═CH-cycPr 1559 5,6-OCH₂O— CF₃ CH₂CH═CH-2-furanyl 1560 5,6-OCH₂O— CF₃ CH═CHCH₂-cycPr 1561 5,6-OCH₂O— CF₃ CH═CHCH₂-2-furanyl 1601 5-Cl CF₂CF₃ CH₂CH₂CH₃ 1602 5-Cl CF₂CF₃ CH₂CH₂CH₂CH₃ 1603 5-Cl CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 1604 5-Cl CF₂CF₃ CH₂CH₂CH(CH₃)₂ 1605 5-Cl CF₂CF₃ CH₂CH₂-tBu 1606 5-Cl CF₂CF₃ CH₂-cycPr 1607 5-Cl CF₂CF₃ CH₂—Ph 1608 5-Cl CF₂CF₃ CH₂-2-Pyridyl 1609 5-Cl CF₂CF₃ CH₂-3-Pyridyl 1610 5-Cl CF₂CF₃ CH₂-4-Pyridyl 1611 5-Cl CF₂CF₃ CH₂-2-furanyl 1612 5-Cl CF₂CF₃ CH₂-3-furanyl 1613 5-Cl CF₂CF₃ CH₂-2-thienyl 1614 5-Cl CF₂CF₃ CH₂-3-thienyl 1615 5-Cl CF₂CF₃ CH₂CH₂-cycPr 1616 5-Cl CF₂CF₃ CH₂CH₂—Ph 1617 5-Cl CF₂CF₃ CH₂CH₂-2-Pyridyl 1618 5-Cl CF₂CF₃ CH₂CH₂-3-Pyridyl 1619 5-Cl CF₂CF₃ CH₂CH₂-4-Pyridyl 1620 5-Cl CF₂CF₃ CH₂CH₂-2-furanyl 1621 5-Cl CF₂CF₃ CH₂CH₂-3-furanyl 1622 5-Cl CF₂CF₃ CH₂CH₂-2-thienyl 1623 5-Cl CF₂CF₃ CH₂CH₂-3-thienyl 1624 5-Cl CF₂CF₃ C≡C—Et 1625 5-Cl CF₂CF₃ C≡C-iPr 1626 5-Cl CF₂CF₃ C≡C-cycPr 1627 5-Cl CF₂CF₃ C≡C-1-(Me)cycPr 1628 5-Cl CF₂CF₃ C≡C-2-pyridyl 1629 5-Cl CF₂CF₃ C≡C-3-pyridyl 1630 5-Cl CF₂CF₃ C≡C-4-pyridyl 1631 5-Cl CF₂CF₃ C≡C-2-furanyl 1632 5-Cl CF₂CF₃ C≡C-3-furanyl 1633 5-Cl CF₂CF₃ C≡C-2-thienyl 1634 5-Cl CF₂CF₃ C≡C-3-thienyl 1635 5-Cl CF₂CF₃ CH═CH—Et 1636 5-Cl CF₂CF₃ CH═CH-iPr 1637 5-Cl CF₂CF₃ CH═CH-cycPr 1638 5-Cl CF₂CF₃ CH═CH-1-(Me)cycPr 1639 5-Cl CF₂CF₃ CH═CH-2-pyridyl 1640 5-Cl CF₂CF₃ CH═CH-3-pyridyl 1641 5-Cl CF₂CF₃ CH═CH-4-pyridyl 1642 5-Cl CF₂CF₃ CH═CH-2-furanyl 1643 5-Cl CF₂CF₃ CH═CH-3-furanyl 1644 5-Cl CF₂CF₃ CH═CH-2-thienyl 1645 5-Cl CF₂CF₃ CH═CH-3-thienyl 1646 5-Cl CF₂CF₃ CH₂—C≡C-cycPr 1647 5-Cl CF₂CF₃ CH₂—C≡C-2-furanyl 1648 5-Cl CF₂CF₃ CH₂CH═CH-cycPr 1649 5-Cl CF₂CF₃ CH₂CH═CH-2-furanyl 1650 5-Cl CF₂CF₃ CH═CHCH₂-cycPr 1651 5-Cl CF₂CF₃ CH═CHCH₂-2-furanyl 1652 6-Cl CF₂CF₃ CH₂CH₂CH₃ 1653 6-Cl CF₂CF₃ CH₂CH₂CH₂CH₃ 1654 6-Cl CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 1655 6-Cl CF₂CF₃ CH₂CH₂CH(CH₃)₂ 1656 6-Cl CF₂CF₃ CH₂CH₂-tBu 1657 6-Cl CF₂CF₃ CH₂-cycPr 1658 6-Cl CF₂CF₃ CH₂—Ph 1659 6-Cl CF₂CF₃ CH₂-2-Pyridyl 1660 6-Cl CF₂CF₃ CH₂-3-Pyridyl 1661 6-Cl CF₂CF₃ CH₂-4-Pyridyl 1662 6-Cl CF₂CF₃ CH₂-2-furanyl 1663 6-Cl CF₂CF₃ CH₂-3-furanyl 1664 6-Cl CF₂CF₃ CH₂-2-thienyl 1665 6-Cl CF₂CF₃ CH₂-3-thienyl 1666 6-Cl CF₂CF₃ CH₂CH₂-cycPr 1667 6-Cl CF₂CF₃ CH₂CH₂—Ph 1668 6-Cl CF₂CF₃ CH₂CH₂-2-Pyridyl 1669 6-Cl CF₂CF₃ CH₂CH₂-3-Pyridyl 1670 6-Cl CF₂CF₃ CH₂CH₂-4-Pyridyl 1671 6-Cl CF₂CF₃ CH₂CH₂-2-furanyl 1672 6-Cl CF₂CF₃ CH₂CH₂-3-furanyl 1673 6-Cl CF₂CF₃ CH₂CH₂-2-thienyl 1674 6-Cl CF₂CF₃ CH₂CH₂-3-thienyl 1675 6-Cl CF₂CF₃ C≡C—Et 1676 6-Cl CF₂CF₃ C≡C-iPr 1677 6-Cl CF₂CF₃ C≡C-cycPr 1678 6-Cl CF₂CF₃ C≡C-1-(Me)cycPr 1679 6-Cl CF₂CF₃ C≡C-2-pyridyl 1680 6-Cl CF₂CF₃ C≡C-3-pyridyl 1681 6-Cl CF₂CF₃ C≡C-4-pyridyl 1682 6-Cl CF₂CF₃ C≡C-2-furanyl 1683 6-Cl CF₂CF₃ C≡C-3-furanyl 1684 6-Cl CF₂CF₃ C≡C-2-thienyl 1685 6-Cl CF₂CF₃ C≡C-3-thienyl 1686 6-Cl CF₂CF₃ CH═CH—Et 1687 6-Cl CF₂CF₃ CH═CH-iPr 1688 6-Cl CF₂CF₃ CH═CH-cycPr 1689 6-Cl CF₂CF₃ CH═CH-1-(Me)cycPr 1690 6-Cl CF₂CF₃ CH═CH-2-pyridyl 1691 6-Cl CF₂CF₃ CH═CH-3-pyridyl 1692 6-Cl CF₂CF₃ CH═CH-4-pyridyl 1693 6-Cl CF₂CF₃ CH═CH-2-furanyl 1694 6-Cl CF₂CF₃ CH═CH-3-furanyl 1695 6-Cl CF₂CF₃ CH═CH-2-thienyl 1696 6-Cl CF₂CF₃ CH═CH-3-thienyl 1697 6-Cl CF₂CF₃ CH₂—C≡C-cycPr 1698 6-Cl CF₂CF₃ CH₂—C≡C-2-furanyl 1699 6-Cl CF₂CF₃ CH₂CH═CH-cycPr 1700 6-Cl CF₂CF₃ CH₂CH═CH-2-furanyl 1701 6-Cl CF₂CF₃ CH═CHCH₂-cycPr 1702 6-Cl CF₂CF₃ CH═CHCH₂-2-furanyl 1703 5-F CF₂CF₃ CH₂CH₂CH₃ 1704 5-F CF₂CF₃ CH₂CH₂CH₂CH₃ 1705 5-F CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 1706 5-F CF₂CF₃ CH₂CH₂CH(CH₃)₂ 1707 5-F CF₂CF₃ CH₂CH₂-tBu 1708 5-F CF₂CF₃ CH₂-cycPr 1709 5-F CF₂CF₃ CH₂—Ph 1710 5-F CF₂CF₃ CH₂-2-Pyridyl 1711 5-F CF₂CF₃ CH₂-3-Pyridyl 1712 5-F CF₂CF₃ CH₂-4-Pyridyl 1713 5-F CF₂CF₃ CH₂-2-furanyl 1714 5-F CF₂CF₃ CH₂-3-furanyl 1715 5-F CF₂CF₃ CH₂-2-thienyl 1716 5-F CF₂CF₃ CH₂-3-thienyl 1717 5-F CF₂CF₃ CH₂CH₂-cycPr 1718 5-F CF₂CF₃ CH₂CH₂—Ph 1719 5-F CF₂CF₃ CH₂CH₂-2-Pyridyl 1720 5-F CF₂CF₃ CH₂CH₂-3-Pyridyl 1721 5-F CF₂CF₃ CH₂CH₂-4-Pyridyl 1722 5-F CF₂CF₃ CH₂CH₂-2-furanyl 1723 5-F CF₂CF₃ CH₂CH₂-3-furanyl 1724 5-F CF₂CF₃ CH₂CH₂-2-thienyl 1725 5-F CF₂CF₃ CH₂CH₂-3-thienyl 1726 5-F CF₂CF₃ C≡C—Et 1727 5-F CF₂CF₃ C≡C-iPr 1728 5-F CF₂CF₃ C≡C-cycPr 1729 5-F CF₂CF₃ C≡C-1-(Me)cycPr 1730 5-F CF₂CF₃ C≡C-2-pyridyl 1731 5-F CF₂CF₃ C≡C-3-pyridyl 1732 5-F CF₂CF₃ C≡C-4-pyridyl 1733 5-F CF₂CF₃ C≡C-2-furanyl 1734 5-F CF₂CF₃ C≡C-3-furanyl 1735 5-F CF₂CF₃ C≡C-2-thienyl 1736 5-F CF₂CF₃ C≡C-3-thienyl 1737 5-F CF₂CF₃ CH═CH—Et 1738 5-F CF₂CF₃ CH═CH-iPr 1739 5-F CF₂CF₃ CH═CH-cycPr 1740 5-F CF₂CF₃ CH═CH-1-(Me)cycPr 1741 5-F CF₂CF₃ CH═CH-2-pyridyl 1742 5-F CF₂CF₃ CH═CH-3-pyridyl 1743 5-F CF₂CF₃ CH═CH-4-pyridyl 1744 5-F CF₂CF₃ CH═CH-2-furanyl 1745 5-F CF₂CF₃ CH═CH-3-furanyl 1746 5-F CF₂CF₃ CH═CH-2-thienyl 1747 5-F CF₂CF₃ CH═CH-3-thienyl 1748 5-F CF₂CF₃ CH₂—C≡C-cycPr 1749 5-F CF₂CF₃ CH₂—C≡C-2-furanyl 1750 5-F CF₂CF₃ CH₂CH═CH-cycPr 1751 5-F CF₂CF₃ CH₂CH═CH-2-furanyl 1752 5-F CF₂CF₃ CH═CHCH₂-cycPr 1753 5-F CF₂CF₃ CH═CHCH₂-2-furanyl 1754 6-F CF₂CF₃ CH₂CH₂CH₃ 1755 6-F CF₂CF₃ CH₂CH₂CH₂CH₃ 1756 6-F CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 1757 6-F CF₂CF₃ CH₂CH₂CH(CH₃)₂ 1758 6-F CF₂CF₃ CH₂CH₂-tBu 1759 6-F CF₂CF₃ CH₂-cycPr 1760 6-F CF₂CF₃ CH₂—Ph 1761 6-F CF₂CF₃ CH₂-2-Pyridyl 1762 6-F CF₂CF₃ CH₂-3-Pyridyl 1763 6-F CF₂CF₃ CH₂-4-Pyridyl 1764 6-F CF₂CF₃ CH₂-2-furanyl 1765 6-F CF₂CF₃ CH₂-3-furanyl 1766 6-F CF₂CF₃ CH₂-2-thienyl 1767 6-F CF₂CF₃ CH₂-3-thienyl 1768 6-F CF₂CF₃ CH₂CH₂-cycPr 1769 6-F CF₂CF₃ CH₂CH₂—Ph 1770 6-F CF₂CF₃ CH₂CH₂-2-Pyridyl 1771 6-F CF₂CF₃ CH₂CH₂-3-Pyridyl 1772 6-F CF₂CF₃ CH₂CH₂-4-Pyridyl 1773 6-F CF₂CF₃ CH₂CH₂-2-furanyl 1774 6-F CF₂CF₃ CH₂CH₂-3-furanyl 1775 6-F CF₂CF₃ CH₂CH₂-2-thienyl 1776 6-F CF₂CF₃ CH₂CH₂-3-thienyl 1777 6-F CF₂CF₃ C≡C—Et 1778 6-F CF₂CF₃ C≡C-iPr 1779 6-F CF₂CF₃ C≡C-cycPr 1780 6-F CF₂CF₃ C≡C-1-(Me)cycPr 1781 6-F CF₂CF₃ C≡C-2-pyridyl 1782 6-F CF₂CF₃ C≡C-3-pyridyl 1783 6-F CF₂CF₃ C≡C-4-pyridyl 1784 6-F CF₂CF₃ C≡C-2-furanyl 1785 6-F CF₂CF₃ C≡C-3-furanyl 1786 6-F CF₂CF₃ C≡C-2-thienyl 1787 6-F CF₂CF₃ C≡C-3-thienyl 1788 6-F CF₂CF₃ CH═CH—Et 1789 6-F CF₂CF₃ CH═CH-iPr 1790 6-F CF₂CF₃ CH═CH-cycPr 1791 6-F CF₂CF₃ CH═CH-1-(Me)cycPr 1792 6-F CF₂CF₃ CH═CH-2-pyridyl 1793 6-F CF₂CF₃ CH═CH-3-pyridyl 1794 6-F CF₂CF₃ CH═CH-4-pyridyl 1795 6-F CF₂CF₃ CH═CH-2-furanyl 1796 6-F CF₂CF₃ CH═CH-3-furanyl 1797 6-F CF₂CF₃ CH═CH-2-thienyl 1798 6-F CF₂CF₃ CH═CH-3-thienyl 1799 6-F CF₂CF₃ CH₂—C≡C-cycPr 1800 6-F CF₂CF₃ CH₂—C≡C-2-furanyl 1801 6-F CF₂CF₃ CH₂CH═CH-cycPr 1802 6-F CF₂CF₃ CH₂CH═CH-2-furanyl 1803 6-F CF₂CF₃ CH═CHCH₂-cycPr 1804 6-F CF₂CF₃ CH═CHCH₂-2-furanyl 1805 5,6-diCl CF₂CF₃ CH₂CH₂CH₃ 1806 5,6-diCl CF₂CF₃ CH₂CH₂CH₂CH₃ 1807 5,6-diCl CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 1808 5,6-diCl CF₂CF₃ CH₂CH₂CH(CH₃)₂ 1809 5,6-diCl CF₂CF₃ CH₂CH₂-tBu 1810 5,6-diCl CF₂CF₃ CH₂-cycPr 1811 5,6-diCl CF₂CF₃ CH₂—Ph 1812 5,6-diCl CF₂CF₃ CH₂-2-Pyridyl 1813 5,6-diCl CF₂CF₃ CH₂-3-Pyridyl 1814 5,6-diCl CF₂CF₃ CH₂-4-Pyridyl 1815 5,6-diCl CF₂CF₃ CH₂-2-furanyl 1816 5,6-diCl CF₂CF₃ CH₂-3-furanyl 1817 5,6-diCl CF₂CF₃ CH₂-2-thienyl 1818 5,6-diCl CF₂CF₃ CH₂-3-thienyl 1819 5,6-diCl CF₂CF₃ CH₂CH₂-cycPr 1820 5,6-diCl CF₂CF₃ CH₂CH₂—Ph 1821 5,6-diCl CF₂CF₃ CH₂CH₂-2-Pyridyl 1822 5,6-diCl CF₂CF₃ CH₂CH₂-3-Pyridyl 1823 5,6-diCl CF₂CF₃ CH₂CH₂-4-Pyridyl 1824 5,6-diCl CF₂CF₃ CH₂CH₂-2-furanyl 1825 5,6-diCl CF₂CF₃ CH₂CH₂-3-furanyl 1826 5,6-diCl CF₂CF₃ CH₂CH₂-2-thienyl 1827 5,6-diCl CF₂CF₃ CH₂CH₂-3-thienyl 1828 5,6-diCl CF₂CF₃ C≡C—Et 1829 5,6-diCl CF₂CF₃ C≡C-iPr 1830 5,6-diCl CF₂CF₃ C≡C-cycPr 1831 5,6-diCl CF₂CF₃ C≡C-1-(Me)cycPr 1832 5,6-diCl CF₂CF₃ C≡C-2-pyridyl 1833 5,6-diCl CF₂CF₃ C≡C-3-pyridyl 1834 5,6-diCl CF₂CF₃ C≡C-4-pyridyl 1835 5,6-diCl CF₂CF₃ C≡C-2-furanyl 1836 5,6-diCl CF₂CF₃ C≡C-3-furanyl 1837 5,6-diCl CF₂CF₃ C≡C-2-thienyl 1838 5,6-diCl CF₂CF₃ C≡C-3-thienyl 1839 5,6-diCl CF₂CF₃ CH═CH—Et 1840 5,6-diCl CF₂CF₃ CH═CH-iPr 1841 5,6-diCl CF₂CF₃ CH═CH-cycPr 1842 5,6-diCl CF₂CF₃ CH═CH-1-(Me)cycPr 1843 5,6-diCl CF₂CF₃ CH═CH-2-pyridyl 1844 5,6-diCl CF₂CF₃ CH═CH-3-pyridyl 1845 5,6-diCl CF₂CF₃ CH═CH-4-pyridyl 1846 5,6-diCl CF₂CF₃ CH═CH-2-furanyl 1847 5,6-diCl CF₂CF₃ CH═CH-3-furanyl 1848 5,6-diCl CF₂CF₃ CH═CH-2-thienyl 1849 5,6-diCl CF₂CF₃ CH═CH-3-thienyl 1850 5,6-diCl CF₂CF₃ CH₂—C≡C-cycPr 1851 5,6-diCl CF₂CF₃ CH₂—C≡C-2-furanyl 1852 5,6-diCl CF₂CF₃ CH₂CH═CH-cycPr 1853 5,6-diCl CF₂CF₃ CH₂CH═CH-2-furanyl 1854 5,6-diCl CF₂CF₃ CH═CHCH₂-cycPr 1855 5,6-diCl CF₂CF₃ CH═CHCH₂-2-furanyl 1856 5,6-diF CF₂CF₃ CH₂CH₂CH₃ 1857 5,6-diF CF₂CF₃ CH₂CH₂CH₂CH₃ 1858 5,6-diF CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 1859 5,6-diF CF₂CF₃ CH₂CH₂CH(CH₃)₂ 1860 5,6-diF CF₂CF₃ CH₂CH₂-tBu 1861 5,6-diF CF₂CF₃ CH₂-cycPr 1862 5,6-diF CF₂CF₃ CH₂—Ph 1863 5,6-diF CF₂CF₃ CH₂-2-Pyridyl 1864 5,6-diF CF₂CF₃ CH₂-3-Pyridyl 1865 5,6-diF CF₂CF₃ CH₂-4-Pyridyl 1866 5,6-diF CF₂CF₃ CH₂-2-furanyl 1867 5,6-diF CF₂CF₃ CH₂-3-furanyl 1868 5,6-diF CF₂CF₃ CH₂-2-thienyl 1869 5,6-diF CF₂CF₃ CH₂-3-thienyl 1870 5,6-diF CF₂CF₃ CH₂CH₂-cycPr 1871 5,6-diF CF₂CF₃ CH₂CH₂—Ph 1872 5,6-diF CF₂CF₃ CH₂CH₂-2-Pyridyl 1873 5,6-diF CF₂CF₃ CH₂CH₂-3-Pyridyl 1874 5,6-diF CF₂CF₃ CH₂CH₂-4-Pyridyl 1875 5,6-diF CF₂CF₃ CH₂CH₂-2-furanyl 1876 5,6-diF CF₂CF₃ CH₂CH₂-3-furanyl 1877 5,6-diF CF₂CF₃ CH₂CH₂-2-thienyl 1878 5,6-diF CF₂CF₃ CH₂CH₂-3-thienyl 1879 5,6-diF CF₂CF₃ C≡C—Et 1880 5,6-diF CF₂CF₃ C≡C-iPr 1881 5,6-diF CF₂CF₃ C≡C-cycPr 1882 5,6-diF CF₂CF₃ C≡C-1-(Me)cycPr 1883 5,6-diF CF₂CF₃ C≡C-2-pyridyl 1884 5,6-diF CF₂CF₃ C≡C-3-pyridyl 1885 5,6-diF CF₂CF₃ C≡C-4-pyridyl 1886 5,6-diF CF₂CF₃ C≡C-2-furanyl 1887 5,6-diF CF₂CF₃ C≡C-3-furanyl 1888 5,6-diF CF₂CF₃ C≡C-2-thienyl 1889 5,6-diF CF₂CF₃ C≡C-3-thienyl 1890 5,6-diF CF₂CF₃ CH═CH—Et 1891 5,6-diF CF₂CF₃ CH═CH-iPr 1892 5,6-diF CF₂CF₃ CH═CH-cycPr 1893 5,6-diF CF₂CF₃ CH═CH-1-(Me)cycPr 1894 5,6-diF CF₂CF₃ CH═CH-2-pyridyl 1895 5,6-diF CF₂CF₃ CH═CH-3-pyridyl 1896 5,6-diF CF₂CF₃ CH═CH-4-pyridyl 1897 5,6-diF CF₂CF₃ CH═CH-2-furanyl 1898 5,6-diF CF₂CF₃ CH═CH-3-furanyl 1899 5,6-diF CF₂CF₃ CH═CH-2-thienyl 1900 5,6-diF CF₂CF₃ CH═CH-3-thienyl 1901 5,6-diF CF₂CF₃ CH₂—C≡C-cycPr 1902 5,6-diF CF₂CF₃ CH₂—C≡C-2-furanyl 1903 5,6-diF CF₂CF₃ CH₂CH═CH-cycPr 1904 5,6-diF CF₂CF₃ CH₂CH═CH-2-furanyl 1905 5,6-diF CF₂CF₃ CH═CHCH₂-cycPr 1906 5,6-diF CF₂CF₃ CH═CHCH₂-2-furanyl 1907 5-Cl, 6-F CF₂CF₃ CH₂CH₂CH₃ 1908 5-Cl, 6-F CF₂CF₃ CH₂CH₂CH₂CH₃ 1909 5-Cl, 6-F CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 1910 5-Cl, 6-F CF₂CF₃ CH₂CH₂CH(CH₃)₂ 1911 5-Cl, 6-F CF₂CF₃ CH₂CH₂-tBu 1912 5-Cl, 6-F CF₂CF₃ CH₂-cycPr 1913 5-Cl, 6-F CF₂CF₃ CH₂—Ph 1914 5-Cl, 6-F CF₂CF₃ CH₂-2-Pyridyl 1915 5-Cl, 6-F CF₂CF₃ CH₂-3-Pyridyl 1916 5-Cl, 6-F CF₂CF₃ CH₂-4-Pyridyl 1917 5-Cl, 6-F CF₂CF₃ CH₂-2-furanyl 1918 5-Cl, 6-F CF₂CF₃ CH₂-3-furanyl 1919 5-Cl, 6-F CF₂CF₃ CH₂-2-thienyl 1920 5-Cl, 6-F CF₂CF₃ CH₂-3-thienyl 1921 5-Cl, 6-F CF₂CF₃ CH₂CH₂-cycPr 1922 5-Cl, 6-F CF₂CF₃ CH₂CH₂—Ph 1923 5-Cl, 6-F CF₂CF₃ CH₂CH₂-2-Pyridyl 1924 5-Cl, 6-F CF₂CF₃ CH₂CH₂-3-Pyridyl 1925 5-Cl, 6-F CF₂CF₃ CH₂CH₂-4-Pyridyl 1926 5-Cl, 6-F CF₂CF₃ CH₂CH₂-2-furanyl 1927 5-Cl, 6-F CF₂CF₃ CH₂CH₂-3-furanyl 1928 5-Cl, 6-F CF₂CF₃ CH₂CH₂-2-thienyl 1929 5-Cl, 6-F CF₂CF₃ CH₂CH₂-3-thienyl 1930 5-Cl, 6-F CF₂CF₃ C≡C—Et 1931 5-Cl, 6-F CF₂CF₃ C≡C-iPr 1932 5-Cl, 6-F CF₂CF₃ C≡C-cycPr 1933 5-Cl, 6-F CF₂CF₃ C≡C-1-(Me)cycPr 1934 5-Cl, 6-F CF₂CF₃ C≡C-2-pyridyl 1935 5-Cl, 6-F CF₂CF₃ C≡C-3-pyridyl 1936 5-Cl, 6-F CF₂CF₃ C≡C-4-pyridyl 1937 5-Cl, 6-F CF₂CF₃ C≡C-2-furanyl 1938 5-Cl, 6-F CF₂CF₃ C≡C-3-furanyl 1939 5-Cl, 6-F CF₂CF₃ C≡C-2-thienyl 1940 5-Cl, 6-F CF₂CF₃ C≡C-3-thienyl 1941 5-Cl, 6-F CF₂CF₃ CH═CH—Et 1942 5-Cl, 6-F CF₂CF₃ CH═CH-iPr 1943 5-Cl, 6-F CF₂CF₃ CH═CH-cycPr 1944 5-Cl, 6-F CF₂CF₃ CH═CH-1-(Me)cycPr 1945 5-Cl, 6-F CF₂CF₃ CH═CH-2-pyridyl 1946 5-Cl, 6-F CF₂CF₃ CH═CH-3-pyridyl 1947 5-Cl, 6-F CF₂CF₃ CH═CH-4-pyridyl 1948 5-Cl, 6-F CF₂CF₃ CH═CH-2-furanyl 1949 5-Cl, 6-F CF₂CF₃ CH═CH-3-furanyl 1950 5-Cl, 6-F CF₂CF₃ CH═CH-2-thienyl 1951 5-Cl, 6-F CF₂CF₃ CH═CH-3-thienyl 1952 5-Cl, 6-F CF₂CF₃ CH₂—C≡C-cycPr 1953 5-Cl, 6-F CF₂CF₃ CH₂—C≡C-2-furanyl 1954 5-Cl, 6-F CF₂CF₃ CH₂CH═CH-cycPr 1955 5-Cl, 6-F CF₂CF₃ CH₂CH═CH-2-furanyl 1956 5-Cl, 6-F CF₂CF₃ CH═CHCH₂-cycPr 1957 5-Cl, 6-F CF₂CF₃ CH═CHCH₂-2-furanyl 1958 5-F, 6-Cl CF₂CF₃ CH₂CH₂CH₃ 1959 5-F, 6-Cl CF₂CF₃ CH₂CH₂CH₂CH₃ 1960 5-F, 6-Cl CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 1961 5-F, 6-Cl CF₂CF₃ CH₂CH₂CH(CH₃)₂ 1962 5-F, 6-Cl CF₂CF₃ CH₂CH₂-tBu 1963 5-F, 6-Cl CF₂CF₃ CH₂-cycPr 1964 5-F, 6-Cl CF₂CF₃ CH₂—Ph 1965 5-F, 6-Cl CF₂CF₃ CH₂-2-Pyridyl 1966 5-F, 6-Cl CF₂CF₃ CH₂-3-Pyridyl 1967 5-F, 6-Cl CF₂CF₃ CH₂-4-Pyridyl 1968 5-F, 6-Cl CF₂CF₃ CH₂-2-furanyl 1969 5-F, 6-Cl CF₂CF₃ CH₂-3-furanyl 1970 5-F, 6-Cl CF₂CF₃ CH₂-2-thienyl 1971 5-F, 6-Cl CF₂CF₃ CH₂-3-thienyl 1972 5-F, 6-Cl CF₂CF₃ CH₂CH₂-cycPr 1973 5-F, 6-Cl CF₂CF₃ CH₂CH₂—Ph 1974 5-F, 6-Cl CF₂CF₃ CH₂CH₂-2-Pyridyl 1975 5-F, 6-Cl CF₂CF₃ CH₂CH₂-3-Pyridyl 1976 5-F, 6-Cl CF₂CF₃ CH₂CH₂-4-Pyridyl 1977 5-F, 6-Cl CF₂CF₃ CH₂CH₂-2-furanyl 1978 5-F, 6-Cl CF₂CF₃ CH₂CH₂-3-furanyl 1979 5-F, 6-Cl CF₂CF₃ CH₂CH₂-2-thienyl 1980 5-F, 6-Cl CF₂CF₃ CH₂CH₂-3-thienyl 1981 5-F, 6-Cl CF₂CF₃ C≡C—Et 1982 5-F, 6-Cl CF₂CF₃ C≡C-iPr 1983 5-F, 6-Cl CF₂CF₃ C≡C-cycPr 1984 5-F, 6-Cl CF₂CF₃ C≡C-1-(Me)cycPr 1985 5-F, 6-Cl CF₂CF₃ C≡C-2-pyridyl 1986 5-F, 6-Cl CF₂CF₃ C≡C-3-pyridyl 1987 5-F, 6-Cl CF₂CF₃ C≡C-4-pyridyl 1988 5-F, 6-Cl CF₂CF₃ C≡C-2-furanyl 1989 5-F, 6-Cl CF₂CF₃ C≡C-3-furanyl 1990 5-F, 6-Cl CF₂CF₃ C≡C-2-thienyl 1991 5-F, 6-Cl CF₂CF₃ C≡C-3-thienyl 1992 5-F, 6-Cl CF₂CF₃ CH═CH—Et 1993 5-F, 6-Cl CF₂CF₃ CH═CH-iPr 1994 5-F, 6-Cl CF₂CF₃ CH═CH-cycPr 1995 5-F, 6-Cl CF₂CF₃ CH═CH-1-(Me)cycPr 1996 5-F, 6-Cl CF₂CF₃ CH═CH-2-pyridyl 1997 5-F, 6-Cl CF₂CF₃ CH═CH-3-pyridyl 1998 5-F, 6-Cl CF₂CF₃ CH═CH-4-pyridyl 1999 5-F, 6-Cl CF₂CF₃ CH═CH-2-furanyl 2000 5-F, 6-Cl CF₂CF₃ CH═CH-3-furanyl 2001 5-F, 6-Cl CF₂CF₃ CH═CH-2-thienyl 2002 5-F, 6-Cl CF₂CF₃ CH═CH-3-thienyl 2003 5-F, 6-Cl CF₂CF₃ CH₂—C≡C-cycPr 2004 5-F, 6-Cl CF₂CF₃ CH₂—C≡C-2-furanyl 2005 5-F, 6-Cl CF₂CF₃ CH₂CH═CH-cycPr 2006 5-F, 6-Cl CF₂CF₃ CH₂CH═CH-2-furanyl 2007 5-F, 6-Cl CF₂CF₃ CH═CHCH₂-cycPr 2008 5-F, 6-Cl CF₂CF₃ CH═CHCH₂-2-furanyl 2009 6-CH₃ CF₂CF₃ CH₂CH₂CH₃ 2010 6-CH₃ CF₂CF₃ CH₂CH₂CH₂CH₃ 2011 6-CH₃ CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 2012 6-CH₃ CF₂CF₃ CH_(2CH) ₂CH(CH₃)₂ 2013 6-CH₃ CF₂CF₃ CH₂CH₂-tBu 2014 6-CH₃ CF₂CF₃ CH₂-cycPr 2015 6-CH₃ CF₂CF₃ CH₂—Ph 2016 6-CH₃ CF₂CF₃ CH₂-2-Pyridyl 2017 6-CH₃ CF₂CF₃ CH₂-3-Pyridyl 2018 6-CH₃ CF₂CF₃ CH₂-4-Pyridyl 2019 6-CH₃ CF₂CF₃ CH₂-2-furanyl 2020 6-CH₃ CF₂CF₃ CH₂-3-furanyl 2021 6-CH₃ CF₂CF₃ CH₂-2-thienyl 2022 6-CH₃ CF₂CF₃ CH₂-3-thienyl 2023 6-CH₃ CF₂CF₃ CH₂CH₂-cycPr 2024 6-CH₃ CF₂CF₃ CH₂CH₂—Ph 2025 6-CH₃ CF₂CF₃ CH₂CH₂-2-Pyridyl 2026 6-CH₃ CF₂CF₃ CH₂CH₂-3-Pyridyl 2027 6-CH₃ CF₂CF₃ CH₂CH₂-4-Pyridyl 2028 6-CH₃ CF₂CF₃ CH₂CH₂-2-furanyl 2029 6-CH₃ CF₂CF₃ CH₂CH₂-3-furanyl 2030 6-CH₃ CF₂CF₃ CH₂CH₂-2-thienyl 2031 6-CH₃ CF₂CF₃ CH₂CH₂-3-thienyl 2032 6-CH₃ CF₂CF₃ C≡C—Et 2033 6-CH₃ CF₂CF₃ C≡C-iPr 2034 6-CH₃ CF₂CF₃ C≡C-cycPr 2035 6-CH₃ CF₂CF₃ C≡C-1-(Me)cycPr 2036 6-CH₃ CF₂CF₃ C≡C-2-pyridyl 2037 6-CH₃ CF₂CF₃ C≡C-3-pyridyl 2038 6-CH₃ CF₂CF₃ C≡C-4-pyridyl 2039 6-CH₃ CF₂CF₃ C≡C-2-furanyl 2040 6-CH₃ CF₂CF₃ C≡C-3-furanyl 2041 6-CH₃ CF₂CF₃ C≡C-2-thienyl 2042 6-CH₃ CF₂CF₃ C≡C-3-thienyl 2043 6-CH₃ CF₂CF₃ CH═CH—Et 2044 6-CH₃ CF₂CF₃ CH═CH-iPr 2045 6-CH₃ CF₂CF₃ CH═CH-cycPr 2046 6-CH₃ CF₂CF₃ CH═CH-1-(Me)cycPr 2047 6-CH₃ CF₂CF₃ CH═CH-2-pyridyl 2048 6-CH₃ CF₂CF₃ CH═CH-3-pyridyl 2049 6-CH₃ CF₂CF₃ CH═CH-4-pyridyl 2050 6-CH₃ CF₂CF₃ CH═CH-2-furanyl 2051 6-CH₃ CF₂CF₃ CH═CH-3-furanyl 2052 6-CH₃ CF₂CF₃ CH═CH-2-thienyl 2053 6-CH₃ CF₂CF₃ CH═CH-3-thienyl 2054 6-CH₃ CF₂CF₃ CH₂—C≡C-cycPr 2055 6-CH₃ CF₂CF₃ CH₂—C≡C-2-furanyl 2056 6-CH₃ CF₂CF₃ CH₂CH═CH-cycPr 2057 6-CH₃ CF₂CF₃ CH₂CH═CH-2-furanyl 2058 6-CH₃ CF₂CF₃ CH═CHCH₂-cycPr 2059 6-CH₃ CF₂CF₃ CH═CHCH₂-2-furanyl 2060 6-OCH₃ CF₂CF₃ CH₂CH₂CH₃ 2061 6-OCH₃ CF₂CF₃ CH₂CH₂CH₂CH₃ 2062 6-OCH₃ CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 2063 6-OCH₃ CF₂CF₃ CH₂CH₂CH(CH₃)₂ 2064 6-OCH₃ CF₂CF₃ CH₂CH₂-tBu 2065 6-OCH₃ CF₂CF₃ CH₂-cycPr 2066 6-OCH₃ CF₂CF₃ CH₂—Ph 2067 6-OCH₃ CF₂CF₃ CH₂-2-Pyridyl 2078 6-OCH₃ CF₂CF₃ CH₂-3-Pyridyl 2079 6-OCH₃ CF₂CF₃ CH₂-4-Pyridyl 2070 6-OCH₃ CF₂CF₃ CH₂-2-furanyl 2071 6-OCH₃ CF₂CF₃ CH₂-3-furanyl 2072 6-OCH₃ CF₂CF₃ CH₂-2-thienyl 2073 6-OCH₃ CF₂CF₃ CH₂-3-thienyl 2074 6-OCH₃ CF₂CF₃ CH₂CH₂-cycPr 2075 6-OCH₃ CF₂CF₃ CH₂CH₂—Ph 2076 6-OCH₃ CF₂CF₃ CH₂CH₂-2-Pyridyl 2077 6-OCH₃ CF₂CF₃ CH₂CH₂-3-Pyridyl 2088 6-OCH₃ CF₂CF₃ CH₂CH₂-4-Pyridyl 2089 6-OCH₃ CF₂CF₃ CH₂CH₂-2-furanyl 2080 6-OCH₃ CF₂CF₃ CH₂CH₂-3-furanyl 2081 6-OCH₃ CF₂CF₃ CH₂CH₂-2-thienyl 2082 6-OCH₃ CF₂CF₃ CH₂CH₂-3-thienyl 2083 6-OCH₃ CF₂CF₃ C≡C—Et 2084 6-OCH₃ CF₂CF₃ C≡C-iPr 2085 6-OCH₃ CF₂CF₃ C≡C-cycPr 2086 6-OCH₃ CF₂CF₃ C≡C-1-(Me)cycPr 2087 6-OCH₃ CF₂CF₃ C≡C-2-pyridyl 2088 6-OCH₃ CF₂CF₃ C≡C-3-pyridyl 2089 6-OCH₃ CF₂CF₃ C≡C-4-pyridyl 2090 6-OCH₃ CF₂CF₃ C≡C-2-furanyl 2091 6-OCH₃ CF₂CF₃ C≡C-3-furanyl 2092 6-OCH₃ CF₂CF₃ C≡C-2-thienyl 2093 6-OCH₃ CF₂CF₃ C≡C-3-thienyl 2094 6-OCH₃ CF₂CF₃ CH═CH—Et 2095 6-OCH₃ CF₂CF₃ CH═CH-iPr 2096 6-OCH₃ CF₂CF₃ CH═CH-cycPr 2097 6-OCH₃ CF₂CF₃ CH═CH-1-(Me)cycPr 2098 6-OCH₃ CF₂CF₃ CH═CH-2-pyridyl 2099 6-OCH₃ CF₂CF₃ CH═CH-3-pyridyl 2100 6-OCH₃ CF₂CF₃ CH═CH-4-pyridyl 2101 6-OCH₃ CF₂CF₃ CH═CH-2-furanyl 2102 6-OCH₃ CF₂CF₃ CH═CH-3-furanyl 2103 6-OCH₃ CF₂CF₃ CH═CH-2-thienyl 2104 6-OCH₃ CF₂CF₃ CH═CH-3-thienyl 2105 6-OCH₃ CF₂CF₃ CH₂—C≡C-cycPr 2106 6-OCH₃ CF₂CF₃ CH₂—C≡C-2-furanyl 2107 6-OCH₃ CF₂CF₃ CH₂CH═CH-cycPr 2108 6-OCH₃ CF₂CF₃ CH₂CH═CH-2-furanyl 2109 6-OCH₃ CF₂CF₃ CH═CHCH₂-cycPr 2110 6-OCH₃ CF₂CF₃ CH═CHCH₂-2-furanyl 2111 5,6-OCH₂O— CF₂CF₃ CH₂CH₂CH₃ 2112 5,6-OCH₂O— CF₂CF₃ CH₂CH₂CH₂CH₃ 2113 5,6-OCH₂O— CF₂CF₃ CH₂CH₂CH₂CH₂CH₃ 2114 5,6-OCH₂O— CF₂CF₃ CH₂CH₂CH(CH₃)₂ 2115 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-tBu 2116 5,6-OCH₂O— CF₂CF₃ CH₂-cycPr 2117 5,6-OCH₂O— CF₂CF₃ CH₂—Ph 2118 5,6-OCH₂O— CF₂CF₃ CH₂-2-Pyridyl 2119 5,6-OCH₂O— CF₂CF₃ CH₂-3-Pyridyl 2120 5,6-OCH₂O— CF₂CF₃ CH₂-4-Pyridyl 2121 5,6-OCH₂O— CF₂CF₃ CH₂-2-furanyl 2122 5,6-OCH₂O— CF₂CF₃ CH₂-3-furanyl 2123 5,6-OCH₂O— CF₂CF₃ CH₂-2-thienyl 2124 5,6-OCH₂O— CF₂CF₃ CH₂-3-thienyl 2125 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-cycPr 2126 5,6-OCH₂O— CF₂CF₃ CH₂CH₂—Ph 2127 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-2-Pyridyl 2128 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-3-Pyridyl 2129 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-4-Pyridyl 2130 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-2-furanyl 2131 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-3-furanyl 2132 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-2-thienyl 2133 5,6-OCH₂O— CF₂CF₃ CH₂CH₂-3-thienyl 2134 5,6-OCH₂O— CF₂CF₃ C≡C—Et 2135 5,6-OCH₂O— CF₂CF₃ C≡C-iPr 2136 5,6-OCH₂O— CF₂CF₃ C≡C-cycPr 2137 5,6-OCH₂O— CF₂CF₃ C≡C-1-(Me)cycPr 2138 5,6-OCH₂O— CF₂CF₃ C≡C-2-pyridyl 2139 5,6-OCH₂O— CF₂CF₃ C≡C-3-pyridyl 2140 5,6-OCH₂O— CF₂CF₃ C≡C-4-pyridyl 2141 5,6-OCH₂O— CF₂CF₃ C≡C-2-furanyl 2142 5,6-OCH₂O— CF₂CF₃ C≡C-3-furanyl 2143 5,6-OCH₂O— CF₂CF₃ C≡C-2-thienyl 2144 5,6-OCH₂O— CF₂CF₃ C≡C-3-thienyl 2145 5,6-OCH₂O— CF₂CF₃ CH═CH—Et 2146 5,6-OCH₂O— CF₂CF₃ CH═CH-iPr 2147 5,6-OCH₂O— CF₂CF₃ CH═CH-cycPr 2148 5,6-OCH₂O— CF₂CF₃ CH═CH-1-(Me)cycPr 2149 5,6-OCH₂O— CF₂CF₃ CH═CH-2-pyridyl 2150 5,6-OCH₂O— CF₂CF₃ CH═CH-3-pyridyl 2151 5,6-OCH₂O— CF₂CF₃ CH═CH-4-pyridyl 2152 5,6-OCH₂O— CF₂CF₃ CH═CH-2-furanyl 2153 5,6-OCH₂O— CF₂CF₃ CH═CH-3-furanyl 2154 5,6-OCH₂O— CF₂CF₃ CH═CH-2-thienyl 2155 5,6-OCH₂O— CF₂CF₃ CH═CH-3-thienyl 2156 5,6-OCH₂O— CF₂CF₃ CH₂—C≡C-cycPr 2157 5,6-OCH₂O— CF₂CF₃ CH₂—C≡C-2-furanyl 2158 5,6-OCH₂O— CF₂CF₃ CH₂CH═CH-cycPr 2159 5,6-OCH₂O— CF₂CF₃ CH₂CH═CH-2-furanyl 2160 5,6-OCH₂O— CF₂CF₃ CH═CHCH₂-cycPr 2161 5,6-OCH₂O— CF₂CF₃ CH═CHCH₂-2-furanyl 2201 5-Cl cycPr CH₂CH₂CH₃ 2202 5-Cl cycPr CH₂CH₂CH₂CH₃ 2203 5-Cl cycPr CH₂CH₂CH₂CH₂CH₃ 2204 5-Cl cycPr CH₂CH₂CH(CH₃)₂ 2205 5-Cl cycPr CH₂CH₂-tBu 2206 5-Cl cycPr CH₂-cycPr 2207 5-Cl cycPr CH₂—Ph 2208 5-Cl cycPr CH₂-2-Pyridyl 2209 5-Cl cycPr CH₂-3-Pyridyl 2210 5-Cl cycPr CH₂-4-Pyridyl 2211 5-Cl cycPr CH₂-2-furanyl 2212 5-Cl cycPr CH₂-3-furanyl 2213 5-Cl cycPr CH₂-2-thienyl 2214 5-Cl cycPr CH₂-3-thienyl 2215 5-Cl cycPr CH₂CH₂-cycPr 2216 5-Cl cycPr CH₂CH₂—Ph 2217 5-Cl cycPr CH₂CH₂-2-Pyridyl 2218 5-Cl cycPr CH₂CH₂-3-Pyridyl 2219 5-Cl cycPr CH₂CH₂-4-Pyridyl 2220 5-Cl cycPr CH₂CH₂-2-furanyl 2221 5-Cl cycPr CH₂CH₂-3-furanyl 2222 5-Cl cycPr CH₂CH₂-2-thienyl 2223 5-Cl cycPr CH₂CH₂-3-thienyl 2224 5-Cl cycPr C≡C—Et 2225 5-Cl cycPr C≡C-iPr 2226 5-Cl cycPr C≡C-cycPr 2227 5-Cl cycPr C≡C-1-(Me)cycPr 2228 5-Cl cycPr C≡C-2-pyridyl 2229 5-Cl cycPr C≡C-3-pyridyl 2230 5-Cl cycPr C≡C-4-pyridyl 2231 5-Cl cycPr C≡C-2-furanyl 2232 5-Cl cycPr C≡C-3-furanyl 2233 5-Cl cycPr C≡C-2-thienyl 2234 5-Cl cycPr C≡C-3-thienyl 2235 5-Cl cycPr CH═CH—Et 2236 5-Cl cycPr CH═CH-iPr 2237 5-Cl cycPr CH═CH-cycPr 2238 5-Cl cycPr CH═CH-1-(Me)cycPr 2239 5-Cl cycPr CH═CH-2-pyridyl 2240 5-Cl cycPr CH═CH-3-pyridyl 2241 5-Cl cycPr CH═CH-4-pyridyl 2242 5-Cl cycPr CH═CH-2-furanyl 2243 5-Cl cycPr CH═CH-3-furanyl 2244 5-Cl cycPr CH═CH-2-thienyl 2245 5-Cl cycPr CH═CH-3-thienyl 2246 5-Cl cycPr CH₂—C≡C-cycPr 2247 5-Cl cycPr CH₂—C≡C-2-furanyl 2248 5-Cl cycPr CH₂CH═CH-cycPr 2249 5-Cl cycPr CH₂CH═CH-2-furanyl 2250 5-Cl cycPr CH═CHCH₂-cycPr 2251 5-Cl cycPr CH═CHCH₂-2-furanyl 2252 6-Cl cycPr CH₂CH₂CH₃ 2253 6-Cl cycPr CH₂CH₂CH₂CH₃ 2254 6-Cl cycPr CH₂CH₂CH₂CH₂CH₃ 2255 6-Cl cycPr CH₂CH₂CH(CH₃)₂ 2256 6-Cl cycPr CH₂CH₂-tBu 2257 6-Cl cycPr CH₂-cycPr 2258 6-Cl cycPr CH₂—Ph 2259 6-Cl cycPr CH₂-2-Pyridyl 2260 6-Cl cycPr CH₂-3-Pyridyl 2261 6-Cl cycPr CH₂-4-Pyridyl 2262 6-Cl cycPr CH₂-2-furanyl 2263 6-Cl cycPr CH₂-3-furanyl 2264 6-Cl cycPr CH₂-2-thienyl 2265 6-Cl cycPr CH₂-3-thienyl 2266 6-Cl cycPr CH₂CH₂-cycPr 2267 6-Cl cycPr CH₂CH₂—Ph 2268 6-Cl cycPr CH₂CH₂-2-Pyridyl 2269 6-Cl cycPr CH₂CH₂-3-Pyridyl 2270 6-Cl cycPr CH₂CH₂-4-Pyridyl 2271 6-Cl cycPr CH₂CH₂-2-furanyl 2272 6-Cl cycPr CH₂CH₂-3-furanyl 2273 6-Cl cycPr CH₂CH₂-2-thienyl 2274 6-Cl cycPr CH₂CH₂-3-thienyl 2275 6-Cl cycPr C≡C—Et 2276 6-Cl cycPr C≡C-iPr 2277 6-Cl cycPr C≡C-cycPr 2278 6-Cl cycPr C≡C-1-(Me)cycPr 2279 6-Cl cycPr C≡C-2-pyridyl 2280 6-Cl cycPr C≡C-3-pyridyl 2281 6-Cl cycPr C≡C-4-pyridyl 2282 6-Cl cycPr C≡C-2-furanyl 2283 6-Cl cycPr C≡C-3-furanyl 2284 6-Cl cycPr C≡C-2-thienyl 2285 6-Cl cycPr C≡C-3-thienyl 2286 6-Cl cycPr CH═CH—Et 2287 6-Cl cycPr CH═CH-iPr 2288 6-Cl cycPr CH═CH-cycPr 2289 6-Cl cycPr CH═CH-1-(Me)cycPr 2290 6-Cl cycPr CH═CH-2-pyridyl 2291 6-Cl cycPr CH═CH-3-pyridyl 2292 6-Cl cycPr CH═CH-4-pyridyl 2293 6-Cl cycPr CH═CH-2-furanyl 2294 6-Cl cycPr CH═CH-3-furanyl 2295 6-Cl cycPr CH═CH-2-thienyl 2296 6-Cl cycPr CH═CH-3-thienyl 2297 6-Cl cycPr CH₂—C≡C-cycPr 2298 6-Cl cycPr CH₂—C≡C-2-furanyl 2299 6-Cl cycPr CH₂CH═CH-cycPr 2300 6-Cl cycPr CH₂CH═CH-2-furanyl 2301 6-Cl cycPr CH═CHCH₂-cycPr 2302 6-Cl cycPr CH═CHCH₂-2-furanyl 2303 5-F cycPr CH₂CH₂CH₃ 2304 5-F cycPr CH₂CH₂CH₂CH₃ 2305 5-F cycPr CH₂CH₂CH₂CH₂CH₃ 2306 5-F cycPr CH₂CH₂CH(CH₃)₂ 2307 5-F cycPr CH₂CH₂-tBu 2308 5-F cycPr CH₂-cycPr 2309 5-F cycPr CH₂—Ph 2310 5-F cycPr CH₂-2-Pyridyl 2311 5-F cycPr CH₂-3-Pyridyl 2312 5-F cycPr CH₂-4-Pyridyl 2313 5-F cycPr CH₂-2-furanyl 2314 5-F cycPr CH₂-3-furanyl 2315 5-F cycPr CH₂-2-thienyl 2316 5-F cycPr CH₂-3-thienyl 2317 5-F cycPr CH₂CH₂-cycPr 2318 5-F cycPr CH₂CH₂—Ph 2319 5-F cycPr CH₂CH₂-2-Pyridyl 2320 5-F cycPr CH₂CH₂-3-Pyridyl 2321 5-F cycPr CH₂CH₂-4-Pyridyl 2322 5-F cycPr CH₂CH₂-2-furanyl 2323 5-F cycPr CH₂CH₂-3-furanyl 2324 5-F cycPr CH₂CH₂-2-thienyl 2325 5-F cycPr CH₂CH₂-3-thienyl 2326 5-F cycPr C≡C—Et 2327 5-F cycPr C≡C-iPr 2328 5-F cycPr C≡C-cycPr 2329 5-F cycPr C≡C-1-(Me)cycPr 2330 5-F cycPr C≡C-2-pyridyl 2331 5-F cycPr C≡C-3-pyridyl 2332 5-F cycPr C≡C-4-pyridyl 2333 5-F cycPr C≡C-2-furanyl 2334 5-F cycPr C≡C-3-furanyl 2335 5-F cycPr C≡C-2-thienyl 2336 5-F cycPr C≡C-3-thienyl 2337 5-F cycPr CH═CH—Et 2338 5-F cycPr CH═CH-iPr 2339 5-F cycPr CH═CH-cycPr 2340 5-F cycPr CH═CH-1-(Me)cycPr 2341 5-F cycPr CH═CH-2-pyridyl 2342 5-F cycPr CH═CH-3-pyridyl 2343 5-F cycPr CH═CH-4-pyridyl 2344 5-F cycPr CH═CH-2-furanyl 2345 5-F cycPr CH═CH-3-furanyl 2346 5-F cycPr CH═CH-2-thienyl 2347 5-F cycPr CH═CH-3-thienyl 2348 5-F cycPr CH₂—C≡C-cycPr 2349 5-F cycPr CH₂—C≡C-2-furanyl 2350 5-F cycPr CH₂CH═CH-cycPr 2351 5-F cycPr CH₂CH═CH-2-furanyl 2352 5-F cycPr CH═CHCH₂-cycPr 2353 5-F cycPr CH═CHCH₂-2-furanyl 2354 6-F cycPr CH₂CH₂CH₃ 2355 6-F cycPr CH₂CH₂CH₂CH₃ 2356 6-F cycPr CH₂CH₂CH₂CH₂CH₃ 2357 6-F cycPr CH₂CH₂CH(CH₃)₂ 2358 6-F cycPr CH₂CH₂-tBu 2359 6-F cycPr CH₂-cycPr 2360 6-F cycPr CH₂—Ph 2361 6-F cycPr CH₂-2-Pyridyl 2362 6-F cycPr CH₂-3-Pyridyl 2363 6-F cycPr CH₂-4-Pyridyl 2364 6-F cycPr CH₂-2-furanyl 2365 6-F cycPr CH₂-3-furanyl 2366 6-F cycPr CH₂-2-thienyl 2367 6-F cycPr CH₂-3-thienyl 2368 6-F cycPr CH₂CH₂-cycPr 2369 6-F cycPr CH₂CH₂—Ph 2370 6-F cycPr CH₂CH₂-2-Pyridyl 2371 6-F cycPr CH₂CH₂-3-Pyridyl 2372 6-F cycPr CH₂CH₂-4-Pyridyl 2373 6-F cycPr CH₂CH₂-2-furanyl 2374 6-F cycPr CH₂CH₂-3-furanyl 2375 6-F cycPr CH₂CH₂-2-thienyl 2376 6-F cycPr CH₂CH₂-3-thienyl 2377 6-F cycPr C≡C—Et 2378 6-F cycPr C≡C-iPr 2379 6-F cycPr C≡C-cycPr 2380 6-F cycPr C≡C-1-(Me)cycPr 2381 6-F cycPr C≡C-2-pyridyl 2382 6-F cycPr C≡C-3-pyridyl 2383 6-F cycPr C≡C-4-pyridyl 2384 6-F cycPr C≡C-2-furanyl 2385 6-F cycPr C≡C-3-furanyl 2386 6-F cycPr C≡C-2-thienyl 2387 6-F cycPr C≡C-3-thienyl 2388 6-F cycPr CH═CH—Et 2389 6-F cycPr CH═CH-iPr 2390 6-F cycPr CH═CH-cycPr 2391 6-F cycPr CH═CH-1-(Me)cycPr 2392 6-F cycPr CH═CH-2-pyridyl 2393 6-F cycPr CH═CH-3-pyridyl 2394 6-F cycPr CH═CH-4-pyridyl 2395 6-F cycPr CH═CH-2-furanyl 2396 6-F cycPr CH═CH-3-furanyl 2397 6-F cycPr CH═CH-2-thienyl 2398 6-F cycPr CH═CH-3-thienyl 2399 6-F cycPr CH₂—C≡C-cycPr 2400 6-F cycPr CH₂—C≡C-2-furanyl 2401 6-F cycPr CH₂CH═CH-cycPr 2402 6-F cycPr CH₂CH═CH-2-furanyl 2403 6-F cycPr CH═CHCH₂-cycPr 2404 6-F cycPr CH═CHCH₂-2-furanyl 2405 5,6-diCl cycPr CH₂CH₂CH₃ 2406 5,6-diCl cycPr CH₂CH₂CH₂CH₃ 2407 5,6-diCl cycPr CH₂CH₂CH₂CH₂CH₃ 2408 5,6-diCl cycPr CH₂CH₂CH(CH₃)₂ 2409 5,6-diCl cycPr CH₂CH₂-tBu 2410 5,6-diCl cycPr CH₂-cycPr 2411 5,6-diCl cycPr CH₂—Ph 2412 5,6-diCl cycPr CH₂-2-Pyridyl 2413 5,6-diCl cycPr CH₂-3-Pyridyl 2414 5,6-diCl cycPr CH₂-4-Pyridyl 2415 5,6-diCl cycPr CH₂-2-furanyl 2416 5,6-diCl cycPr CH₂-3-furanyl 2417 5,6-diCl cycPr CH₂-2-thienyl 2418 5,6-diCl cycPr CH₂-3-thienyl 2419 5,6-diCl cycPr CH₂CH₂-cycPr 2420 5,6-diCl cycPr CH₂CH₂—Ph 2421 5,6-diCl cycPr CH₂CH₂-2-Pyridyl 2422 5,6-diCl cycPr CH₂CH₂-3-Pyridyl 2423 5,6-diCl cycPr CH₂CH₂-4-Pyridyl 2424 5,6-diCl cycPr CH₂CH₂-2-furanyl 2425 5,6-diCl cycPr CH₂CH₂-3-furanyl 2426 5,6-diCl cycPr CH₂CH₂-2-thienyl 2427 5,6-diCl cycPr CH₂CH₂-3-thienyl 2428 5,6-diCl cycPr C≡C—Et 2429 5,6-diCl cycPr C≡C-iPr 2430 5,6-diCl cycPr C≡C-cycPr 2431 5,6-diCl cycPr C≡C-1-(Me)cycPr 2432 5,6-diCl cycPr C≡C-2-pyridyl 2433 5,6-diCl cycPr C≡C-3-pyridyl 2434 5,6-diCl cycPr C≡C-4-pyridyl 2435 5,6-diCl cycPr C≡C-2-furanyl 2436 5,6-diCl cycPr C≡C-3-furanyl 2437 5,6-diCl cycPr C≡C-2-thienyl 2438 5,6-diCl cycPr C≡C-3-thienyl 2439 5,6-diCl cycPr CH═CH—Et 2440 5,6-diCl cycPr CH═CH-iPr 2441 5,6-diCl cycPr CH═CH-cycPr 2442 5,6-diCl cycPr CH═CH-1-(Me)cycPr 2443 5,6-diCl cycPr CH═CH-2-pyridyl 2444 5,6-diCl cycPr CH═CH-3-pyridyl 2445 5,6-diCl cycPr CH═CH-4-pyridyl 2446 5,6-diCl cycPr CH═CH-2-furanyl 2447 5,6-diCl cycPr CH═CH-3-furanyl 2448 5,6-diCl cycPr CH═CH-2-thienyl 2449 5,6-diCl cycPr CH═CH-3-thienyl 2450 5,6-diCl cycPr CH₂—C≡C-cycPr 2451 5,6-diCl cycPr CH₂—C≡C-2-furanyl 2452 5,6-diCl cycPr CH₂CH═CH-cycPr 2453 5,6-diCl cycPr CH₂CH═CH-2-furanyl 2454 5,6-diCl cycPr CH═CHCH₂-cycPr 2455 5,6-diCl cycPr CH═CHCH₂-2-furanyl 2456 5,6-diF cycPr CH₂CH₂CH₃ 2457 5,6-diF cycPr CH₂CH₂CH₂CH₃ 2458 5,6-diF cycPr CH₂CH₂CH₂CH₂CH₃ 2459 5,6-diF cycPr CH₂CH₂CH(CH₃)₂ 2460 5,6-diF cycPr CH₂CH₂-tBu 2461 5,6-diF cycPr CH₂-cycPr 2462 5,6-diF cycPr CH₂—Ph 2463 5,6-diF cycPr CH₂-2-Pyridyl 2464 5,6-diF cycPr CH₂-3-Pyridyl 2465 5,6-diF cycPr CH₂-4-Pyridyl 2466 5,6-diF cycPr CH₂-2-furanyl 2467 5,6-diF cycPr CH₂-3-furanyl 2468 5,6-diF cycPr CH₂-2-thienyl 2469 5,6-diF cycPr CH₂-3-thienyl 2470 5,6-diF cycPr CH₂CH₂-cycPr 2471 5,6-diF cycPr CH₂CH₂—Ph 2472 5,6-diF cycPr CH₂CH₂-2-Pyridyl 2473 5,6-diF cycPr CH₂CH₂-3-Pyridyl 2474 5,6-diF cycPr CH₂CH₂-4-Pyridyl 2475 5,6-diF cycPr CH₂CH₂-2-furanyl 2476 5,6-diF cycPr CH₂CH₂-3-furanyl 2477 5,6-diF cycPr CH₂CH₂-2-thienyl 2478 5,6-diF cycPr CH₂CH₂-3-thienyl 2479 5,6-diF cycPr C≡C—Et 2480 5,6-diF cycPr C≡C-iPr 2481 5,6-diF cycPr C≡C-cycPr 2482 5,6-diF cycPr C≡C-1-(Me)cycPr 2483 5,6-diF cycPr C≡C-2-pyridyl 2484 5,6-diF cycPr C≡C-3-pyridyl 2485 5,6-diF cycPr C≡C-4-pyridyl 2486 5,6-diF cycPr C≡C-2-furanyl 2487 5,6-diF cycPr C≡C-3-furanyl 2488 5,6-diF cycPr C≡C-2-thienyl 2489 5,6-diF cycPr C≡C-3-thienyl 2490 5,6-diF cycPr CH═CH—Et 2491 5,6-diF cycPr CH═CH-iPr 2492 5,6-diF cycPr CH═CH-cycPr 2493 5,6-diF cycPr CH═CH-1-(Me)cycPr 2494 5,6-diF cycPr CH═CH-2-pyridyl 2495 5,6-diF cycPr CH═CH-3-pyridyl 2496 5,6-diF cycPr CH═CH-4-pyridyl 2497 5,6-diF cycPr CH═CH-2-furanyl 2498 5,6-diF cycPr CH═CH-3-furanyl 2499 5,6-diF cycPr CH═CH-2-thienyl 2500 5,6-diF cycPr CH═CH-3-thienyl 2501 5,6-diF cycPr CH₂—C≡C-cycPr 2502 5,6-diF cycPr CH₂—C≡C-2-furanyl 2503 5,6-diF cycPr CH₂CH═CH-cycPr 2504 5,6-diF cycPr CH₂CH═CH-2-furanyl 2505 5,6-diF cycPr CH═CHCH₂-cycPr 2506 5,6-diF cycPr CH═CHCH₂-2-furanyl 2507 5-Cl, 6-F cycPr CH₂CH₂CH₃ 2508 5-Cl, 6-F cycPr CH₂CH₂CH₂CH₃ 2509 5-Cl, 6-F cycPr CH₂CH₂CH₂CH₂CH₃ 2510 5-Cl, 6-F cycPr CH₂CH₂CH(CH₃)₂ 2511 5-Cl, 6-F cycPr CH₂CH₂-tBu 2512 5-Cl, 6-F cycPr CH₂-cycPr 2513 5-Cl, 6-F cycPr CH₂—Ph 2514 5-Cl, 6-F cycPr CH₂-2-Pyridyl 2515 5-Cl, 6-F cycPr CH₂-3-Pyridyl 2516 5-Cl, 6-F cycPr CH₂-4-Pyridyl 2517 5-Cl, 6-F cycPr CH₂-2-furanyl 2518 5-Cl, 6-F cycPr CH₂-3-furanyl 2519 5-Cl, 6-F cycPr CH₂-2-thienyl 2520 5-Cl, 6-F cycPr CH₂-3-thienyl 2521 5-Cl, 6-F cycPr CH₂CH₂-cycPr 2522 5-Cl, 6-F cycPr CH₂CH₂—Ph 2523 5-Cl, 6-F cycPr CH₂CH₂-2-Pyridyl 2524 5-Cl, 6-F cycPr CH₂CH₂-3-Pyridyl 2525 5-Cl, 6-F cycPr CH₂CH₂-4-Pyridyl 2526 5-Cl, 6-F cycPr CH₂CH₂-2-furanyl 2527 5-Cl, 6-F cycPr CH₂CH₂-3-furanyl 2528 5-Cl, 6-F cycPr CH₂CH₂-2-thienyl 2529 5-Cl, 6-F cycPr CH₂CH₂-3-thienyl 2530 5-Cl, 6-F cycPr C≡C—Et 2531 5-Cl, 6-F cycPr C≡C-iPr 2532 5-Cl, 6-F cycPr C≡C-cycPr 2533 5-Cl, 6-F cycPr C≡C-1-(Me)cycPr 2534 5-Cl, 6-F cycPr C≡C-2-pyridyl 2535 5-Cl, 6-F cycPr C≡C-3-pyridyl 2536 5-Cl, 6-F cycPr C≡C-4-pyridyl 2537 5-Cl, 6-F cycPr C≡C-2-furanyl 2538 5-Cl, 6-F cycPr C≡C-3-furanyl 2539 5-Cl, 6-F cycPr C≡C-2-thienyl 2540 5-Cl, 6-F cycPr C≡C-3-thienyl 2541 5-Cl, 6-F cycPr CH═CH—Et 2542 5-Cl, 6-F cycPr CH═CH-iPr 2543 5-Cl, 6-F cycPr CH═CH-cycPr 2544 5-Cl, 6-F cycPr CH═CH-1-(Me)cycPr 2545 5-Cl, 6-F cycPr CH═CH-2-pyridyl 2546 5-Cl, 6-F cycPr CH═CH-3-pyridyl 2547 5-Cl, 6-F cycPr CH═CH-4-pyridyl 2548 5-Cl, 6-F cycPr CH═CH-2-furanyl 2549 5-Cl, 6-F cycPr CH═CH-3-furanyl 2550 5-Cl, 6-F cycPr CH═CH-2-thienyl 2551 5-Cl, 6-F cycPr CH═CH-3-thienyl 2552 5-Cl, 6-F cycPr CH₂—C≡C-cycPr 2553 5-Cl, 6-F cycPr CH₂—C≡C-2-furanyl 2554 5-Cl, 6-F cycPr CH₂CH═CH-cycPr 2555 5-Cl, 6-F cycPr CH₂CH═CH-2-furanyl 2556 5-Cl, 6-F cycPr CH═CHCH₂-cycPr 2557 5-Cl, 6-F cycPr CH═CHCH₂-2-furanyl 2558 5-F, 6-Cl cycPr CH₂CH₂CH₃ 2559 5-F, 6-Cl cycPr CH₂CH₂CH₂CH₃ 2560 5-F, 6-Cl cycPr CH₂CH₂CH₂CH₂CH₃ 2561 5-F, 6-Cl cycPr CH₂CH₂CH(CH₃)₂ 2562 5-F, 6-Cl cycPr CH₂CH₂-tBu 2563 5-F, 6-Cl cycPr CH₂-cycPr 2564 5-F, 6-Cl cycPr CH₂—Ph 2565 5-F, 6-Cl cycPr CH₂-2-Pyridyl 2566 5-F, 6-Cl cycPr CH₂-3-Pyridyl 2567 5-F, 6-Cl cycPr CH₂-4-Pyridyl 2568 5-F, 6-Cl cycPr CH₂-2-furanyl 2569 5-F, 6-Cl cycPr CH₂-3-furanyl 2570 5-F, 6-Cl cycPr CH₂-2-thienyl 2571 5-F, 6-Cl cycPr CH₂-3-thienyl 2572 5-F, 6-Cl cycPr CH₂CH₂-cycPr 2573 5-F, 6-Cl cycPr CH₂CH₂—Ph 2574 5-F, 6-Cl cycPr CH₂CH₂-2-Pyridyl 2575 5-F, 6-Cl cycPr CH₂CH₂-3-Pyridyl 2576 5-F, 6-Cl cycPr CH₂CH₂-4-Pyridyl 2577 5-F, 6-Cl cycPr CH₂CH₂-2-furanyl 2578 5-F, 6-Cl cycPr CH₂CH₂-3-furanyl 2579 5-F, 6-Cl cycPr CH₂CH₂-2-thienyl 2580 5-F, 6-Cl cycPr CH₂CH₂-3-thienyl 2581 5-F, 6-Cl cycPr C≡C—Et 2582 5-F, 6-Cl cycPr C≡C-iPr 2583 5-F, 6-Cl cycPr C≡C-cycPr 2584 5-F, 6-Cl cycPr C≡C-1-(Me)cycPr 2585 5-F, 6-Cl cycPr C≡C-2-pyridyl 2586 5-F, 6-Cl cycPr C≡C-3-pyridyl 2587 5-F, 6-Cl cycPr C≡C-4-pyridyl 2588 5-F, 6-Cl cycPr C≡C-2-furanyl 2589 5-F, 6-Cl cycPr C≡C-3-furanyl 2590 5-F, 6-Cl cycPr C≡C-2-thienyl 2591 5-F, 6-Cl cycPr C≡C-3-thienyl 2592 5-F, 6-Cl cycPr CH═CH—Et 2593 5-F, 6-Cl cycPr CH═CH-iPr 2594 5-F, 6-Cl cycPr CH═CH-cycPr 2595 5-F, 6-Cl cycPr CH═CH-1-(Me)cycPr 2596 5-F, 6-Cl cycPr CH═CH-2-pyridyl 2597 5-F, 6-Cl cycPr CH═CH-3-pyridyl 2598 5-F, 6-Cl cycPr CH═CH-4-pyridyl 2599 5-F, 6-Cl cycPr CH═CH-2-furanyl 2600 5-F, 6-Cl cycPr CH═CH-3-furanyl 2601 5-F, 6-Cl cycPr CH═CH-2-thienyl 2602 5-F, 6-Cl cycPr CH═CH-3-thienyl 2603 5-F, 6-Cl cycPr CH₂—C≡C-cycPr 2604 5-F, 6-Cl cycPr CH₂—C≡C-2-furanyl 2605 5-F, 6-Cl cycPr CH₂CH═CH-cycPr 2606 5-F, 6-Cl cycPr CH₂CH═CH-2-furanyl 2607 5-F, 6-Cl cycPr CH═CHCH₂-cycPr 2608 5-F, 6-Cl cycPr CH═CHCH₂-2-furanyl 2609 6-CH₃ cycPr CH₂CH₂CH₃ 2610 6-CH₃ cycPr CH₂CH₂CH₂CH₃ 2611 6-CH₃ cycPr CH₂CH₂CH₂CH₂CH₃ 2612 6-CH₃ cycPr CH₂CH₂CH(CH₃)₂ 2613 6-CH₃ cycPr CH₂CH₂-tBu 2614 6-CH₃ cycPr CH₂-cycPr 2615 6-CH₃ cycPr CH₂—Ph 2616 6-CH₃ cycPr CH₂-2-Pyridyl 2617 6-CH₃ cycPr CH₂-3-Pyridyl 2618 6-CH₃ cycPr CH₂-4-Pyridyl 2619 6-CH₃ cycPr CH₂-2-furanyl 2620 6-CH₃ cycPr CH₂-3-furanyl 2621 6-CH₃ cycPr CH₂-2-thienyl 2622 6-CH₃ cycPr CH₂-3-thienyl 2623 6-CH₃ cycPr CH₂CH₂-cycPr 2624 6-CH₃ cycPr CH₂CH₂—Ph 2625 6-CH₃ cycPr CH₂CH₂-2-Pyridyl 2626 6-CH₃ cycPr CH₂CH₂-3-Pyridyl 2627 6-CH₃ cycPr CH₂CH₂-4-Pyridyl 2628 6-CH₃ cycPr CH₂CH₂-2-furanyl 2629 6-CH₃ cycPr CH₂CH₂-3-furanyl 2630 6-CH₃ cycPr CH₂CH₂-2-thienyl 2631 6-CH₃ cycPr CH₂CH₂-3-thienyl 2632 6-CH₃ cycPr C≡C—Et 2633 6-CH₃ cycPr C≡C-iPr 2634 6-CH₃ cycPr C≡C-cycPr 2635 6-CH₃ cycPr C≡C-1-(Me)cycPr 2636 6-CH₃ cycPr C≡C-2-pyridyl 2637 6-CH₃ cycPr C≡C-3-pyridyl 2638 6-CH₃ cycPr C≡C-4-pyridyl 2639 6-CH₃ cycPr C≡C-2-furanyl 2640 6-CH₃ cycPr C≡C-3-furanyl 2641 6-CH₃ cycPr C≡C-2-thienyl 2642 6-CH₃ cycPr C≡C-3-thienyl 2643 6-CH₃ cycPr CH═CH—Et 2644 6-CH₃ cycPr CH═CH-iPr 2645 6-CH₃ cycPr CH═CH-cycPr 2646 6-CH₃ cycPr CH═CH-1-(Me)cycPr 2647 6-CH₃ cycPr CH═CH-2-pyridyl 2648 6-CH₃ cycPr CH═CH-3-pyridyl 2649 6-CH₃ cycPr CH═CH-4-pyridyl 2650 6-CH₃ cycPr CH═CH-2-furanyl 2651 6-CH₃ cycPr CH═CH-3-furanyl 2652 6-CH₃ cycPr CH═CH-2-thienyl 2653 6-CH₃ cycPr CH═CH-3-thienyl 2654 6-CH₃ cycPr CH₂—C≡C-cycPr 2655 6-CH₃ cycPr CH₂—C≡C-2-furanyl 2656 6-CH₃ cycPr CH₂CH═CH-cycPr 2657 6-CH₃ cycPr CH₂CH═CH-2-furanyl 2658 6-CH₃ cycPr CH═CHCH₂-cycPr 2659 6-CH₃ cycPr CH═CHCH₂-2-furanyl 2660 6-OCH₃ cycPr CH₂CH₂CH₃ 2661 6-OCH₃ cycPr CH₂CH₂CH₂CH₃ 2662 6-OCH₃ cycPr CH₂CH₂CH₂CH₂CH₃ 2663 6-OCH₃ cycPr CH₂CH₂CH(CH₃)₂ 2664 6-OCH₃ cycPr CH₂CH₂-tBu 2665 6-OCH₃ cycPr CH₂-cycPr 2666 6-OCH₃ cycPr CH₂—Ph 2667 6-OCH₃ cycPr CH₂-2-Pyridyl 2668 6-OCH₃ cycPr CH₂-3-Pyridyl 2669 6-OCH₃ cycPr CH₂-4-Pyridyl 2670 6-OCH₃ cycPr CH₂-2-furanyl 2671 6-OCH₃ cycPr CH₂-3-furanyl 2672 6-OCH₃ cycPr CH₂-2-thienyl 2673 6-OCH₃ cycPr CH₂-3-thienyl 2674 6-OCH₃ cycPr CH₂CH₂-cycPr 2675 6-OCH₃ cycPr CH₂CH₂—Ph 2676 6-OCH₃ cycPr CH₂CH₂-2-Pyridyl 2677 6-OCH₃ cycPr CH₂CH₂-3-Pyridyl 2678 6-OCH₃ cycPr CH₂CH₂-4-Pyridyl 2679 6-OCH₃ cycPr CH₂CH₂-2-furanyl 2680 6-OCH₃ cycPr CH₂CH₂-3-furanyl 2681 6-OCH₃ cycPr CH₂CH₂-2-thienyl 2682 6-OCH₃ cycPr CH₂CH₂-3-thienyl 2683 6-OCH₃ cycPr C≡C—Et 2684 6-OCH₃ cycPr C≡C-iPr 2685 6-OCH₃ cycPr C≡C-cycPr 2686 6-OCH₃ cycPr C≡C-1-(Me)cycPr 2687 6-OCH₃ cycPr C≡C-2-pyridyl 2688 6-OCH₃ cycPr C≡C-3-pyridyl 2689 6-OCH₃ cycPr C≡C-4-pyridyl 2690 6-OCH₃ cycPr C≡C-2-furanyl 2691 6-OCH₃ cycPr C≡C-3-furanyl 2692 6-OCH₃ cycPr C≡C-2-thienyl 2693 6-OCH₃ cycPr C≡C-3-thienyl 2694 6-OCH₃ cycPr CH═CH—Et 2695 6-OCH₃ cycPr CH═CH-iPr 2696 6-OCH₃ cycPr CH═CH-cycPr 2697 6-OCH₃ cycPr CH═CH-1-(Me)cycPr 2698 6-OCH₃ cycPr CH═CH-2-pyridyl 2699 6-OCH₃ cycPr CH═CH-3-pyridyl 2700 6-OCH₃ cycPr CH═CH-4-pyridyl 2701 6-OCH₃ cycPr CH═CH-2-furanyl 2702 6-OCH₃ cycPr CH═CH-3-furanyl 2703 6-OCH₃ cycPr CH═CH-2-thienyl 2704 6-OCH₃ cycPr CH═CH-3-thienyl 2705 6-OCH₃ cycPr CH₂—C≡C-cycPr 2706 6-OCH₃ cycPr CH₂—C≡C-2-furanyl 2707 6-OCH₃ cycPr CH₂CH═CH-cycPr 2708 6-OCH₃ cycPr CH₂CH═CH-2-furanyl 2709 6-OCH₃ cycPr CH═CHCH₂-cycPr 2710 6-OCH₃ cycPr CH═CHCH₂-2-furanyl 2711 5,6-OCH₂O— cycPr CH₂CH₂CH₃ 2712 5,6-OCH₂O— cycPr CH₂CH₂CH₂CH₃ 2713 5,6-OCH₂O— cycPr CH₂CH₂CH₂CH₂CH₃ 2714 5,6-OCH₂O— cycPr CH₂CH₂CH(CH₃)₂ 2715 5,6-OCH₂O— cycPr CH₂CH₂-tBu 2716 5,6-OCH₂O— cycPr CH₂-cycPr 2717 5,6-OCH₂O— cycPr CH₂—Ph 2718 5,6-OCH₂O— cycPr CH₂-2-Pyridyl 2719 5,6-OCH₂O— cycPr CH₂-3-Pyridyl 2720 5,6-OCH₂O— cycPr CH₂-4-Pyridyl 2721 5,6-OCH₂O— cycPr CH₂-2-furanyl 2722 5,6-OCH₂O— cycPr CH₂-3-furanyl 2723 5,6-OCH₂O— cycPr CH₂-2-thienyl 2724 5,6-OCH₂O— cycPr CH₂-3-thienyl 2725 5,6-OCH₂O— cycPr CH₂CH₂-cycPr 2726 5,6-OCH₂O— cycPr CH₂CH₂—Ph 2727 5,6-OCH₂O— cycPr CH₂CH₂-2-Pyridyl 2728 5,6-OCH₂O— cycPr CH₂CH₂-3-Pyridyl 2729 5,6-OCH₂O— cycPr CH₂CH₂-4-Pyridyl 2730 5,6-OCH₂O— cycPr CH₂CH₂-2-furanyl 2731 5,6-OCH₂O— cycPr CH₂CH₂-3-furanyl 2732 5,6-OCH₂O— cycPr CH₂CH₂-2-thienyl 2733 5,6-OCH₂O— cycPr CH₂CH₂-3-thienyl 2734 5,6-OCH₂O— cycPr C≡C—Et 2735 5,6-OCH₂O— cycPr C≡C-iPr 2736 5,6-OCH₂O— cycPr C≡C-cycPr 2737 5,6-OCH₂O— cycPr C≡C-1-(Me)cycPr 2738 5,6-OCH₂O— cycPr C≡C-2-pyridyl 2739 5,6-OCH₂O— cycPr C≡C-3-pyridyl 2740 5,6-OCH₂O— cycPr C≡C-4-pyridyl 2741 5,6-OCH₂O— cycPr C≡C-2-furanyl 2742 5,6-OCH₂O— cycPr C≡C-3-furanyl 2743 5,6-OCH₂O— cycPr C≡C-2-thienyl 2744 5,6-OCH₂O— cycPr C≡C-3-thienyl 2745 5,6-OCH₂O— cycPr CH═CH—Et 2746 5,6-OCH₂O— cycPr CH═CH-iPr 2747 5,6-OCH₂O— cycPr CH═CH-cycPr 2748 5,6-OCH₂O— cycPr CH═CH-1-(Me)cycPr 2749 5,6-OCH₂O— cycPr CH═CH-2-pyridyl 2750 5,6-OCH₂O— cycPr CH═CH-3-pyridyl 2751 5,6-OCH₂O— cycPr CH═CH-4-pyridyl 2752 5,6-OCH₂O— cycPr CH═CH-2-furanyl 2753 5,6-OCH₂O— cycPr CH═CH-3-furanyl 2754 5,6-OCH₂O— cycPr CH═CH-2-thienyl 2755 5,6-OCH₂O— cycPr CH═CH-3-thienyl 2756 5,6-OCH₂O— cycPr CH₂—C≡C-cycPr 2757 5,6-OCH₂O— cycPr CH₂—C≡C-2-furanyl 2758 5,6-OCH₂O— cycPr CH₂CH═CH-cycPr 2759 5,6-OCH₂O— cycPr CH₂CH═CH-2-furanyl 2760 5,6-OCH₂O— cycPr CH═CHCH₂-cycPr 2761 5,6-OCH₂O— cycPr CH═CHCH₂-2-furanyl

TABLE 3

Ex.# W X Y Z R¹ R² 3001 CH CCl CH N CF₃ C≡C-nPr 3002 CH CCl CH N CF₃ C≡C-Bu 3003 CH CCl CH N CF₃ C≡C-iBu 3004 CH CCl CH N CF₃ C≡C-tBu 3005 CH CCl CH N CF₃ C≡C-Et 3006 CH CCl CH N CF₃ C≡C-Me 3007 CH CCl CH N CF₃ C≡C—Ph 3008 CH CCl CH N CF₃ C≡C-cycPr 3009 CH CCl CH N CF₃ C≡C-1-(Me)cycPr 3010 CH CCl CH N CF₃ C≡C-2-Pyridyl 3011 CH CCl CH N CF₃ C≡C-3-Pyridyl 3012 CH CCl CH N CF₃ C≡C-4-Pyridyl 3013 CH CCl CH N CF₃ C≡C-2-furanyl 3014 CH CCl CH N CF₃ C≡C-3-furanyl 3015 CH CCl CH N CF₃ C≡C-2-thienyl 3016 CH CCl CH N CF₃ C≡C-3-thienyl 3017 CH CCl CH N CF₃ CH═CH-cycPr 3018 CH CCl CH N CF₃ CH═CH-ipr 3019 CH CCl CH N CF₃ CH═CH-nPr 3020 CH CCl CH N CF₃ CH═CH-Bu 3021 CH CCl CH N CF₃ CH═CH-iBu 3022 CH CCl CH N CF₃ CH═CH-tBu 3023 CH CCl CH N CF₃ CH═CH-Et 3024 CH CCl CH N CF₃ CH═CH-Me 3025 CH CCl CH N CF₃ CH═CH—Ph 3026 CH CCl CH N CF₃ CH═CH-2-Pyridyl 3027 CH CCl CH N CF₃ CH═CH-3-Pyridyl 3028 CH CCl CH N CF₃ CH═CH-4-Pyridyl 3029 CH CCl CH N CF₃ CH═CH-2-furanyl 3030 CH CCl CH N CF₃ CH═CH-3-furanyl 3031 CH CCl CH N CF₃ CH═CH-2-thienyl 3032 CH CCl CH N CF₃ CH═CH-3-thienyl 3033 CH CCl CH N CF₃ CH₂CH₂CH₂CH₂CH₃ 3034 CH CCl CH N CF₃ CH₂CH₂CH(CH₃)₂ 3035 CH CCl CH N CF₃ CH₂CH₂CH₂CH₃ 3036 CH CCl CH N CF₃ CH₂CH₂CH₃ 3037 CH CCl CH N CF₃ CH₂CH₂-cycPr 3038 CH CCl CH N CF₃ CH₂CH₂-tBu 3039 CH CCl CH N CF₃ CH₂CH₂-2-Pyridyl 3040 CH CCl CH N CF₃ CH₂CH₂-3-Pyridyl 3041 CH CCl CH N CF₃ CH₂CH₂-4-Pyridyl 3042 CH CCl CH N CF₃ CH₂CH₂-2-furanyl 3043 CH CCl CH N CF₃ CH₂CH₂-3-furanyl 3044 CH CCl CH N CF₃ CH₂CH₂-2-thienyl 3045 CH CCl CH N CF₃ CH₂CH₂-3-thienyl 3046 CH C(OCH₃) CH N CF₃ C≡C-cycPr 3047 CH C(OCH₃) CH N CF₃ C≡C-1-(Me)cycPr 3048 CH C(OCH₃) CH N CF₃ C≡C-ipr 3049 CH C(OCH₃) CH N CF₃ C≡C-npr 3050 CH C(OCH₃) CH N CF₃ C≡C-Bu 3051 CH C(OCH₃) CH N CF₃ C≡C-iBu 3052 CH C(OCH₃) CH N CF₃ C≡C-tBu 3053 CH C(OCH₃) CH N CF₃ C≡C-Et 3054 CH C(OCH₃) CH N CF₃ C≡C-Me 3055 CH C(OCH₃) CH N CF₃ C≡C—Ph 3056 CH C(OCH₃) CH N CF₃ C≡C-2-Pyridyl 3057 CH C(OCH₃) CH N CF₃ C≡C-3-Pyridyl 3058 CH C(OCH₃) CH N CF₃ C≡C-4-Pyridyl 3059 CH C(OCH₃) CH N CF₃ C≡C-2-furanyl 3060 CH C(OCH₃) CH N CF₃ C≡C-3-furanyl 3061 CH C(OCH₃) CH N CF₃ C≡C-2-thienyl 3062 CH C(OCH₃) CH N CF₃ C≡C-3-thienyl 3063 CH C(OCH₃) CH N CF₃ CH═CH-cycPr 3064 CH C(OCH₃) CH N CF₃ CH═CH-ipr 3065 CH C(OCH₃) CH N CF₃ CH═CH-npr 3066 CH C(OCH₃) CH N CF₃ CH═CH-Bu 3067 CH C(OCH₃) CH N CF₃ CH═CH-iBu 3068 CH C(OCH₃) CH N CF₃ CH═CH-tBu 3069 CH C(OCH₃) CH N CF₃ CH═CH-Et 3070 CH C(OCH₃) CH N CF₃ CH═CH-Me 3071 CH C(OCH₃) CH N CF₃ CH═CH—Ph 3072 CH C(OCH₃) CH N CF₃ CH═CH-2-Pyridyl 3073 CH C(OCH₃) CH N CF₃ CH═CH-3-Pyridyl 3074 CH C(OCH₃) CH N CF₃ CH═CH-4-Pyridyl 3075 CH C(OCH₃) CH N CF₃ CH═CH-2-furanyl 3076 CH C(OCH₃) CH N CF₃ CH═CH-3-furanyl 3077 CH C(OCH₃) CH N CF₃ CH═CH-2-thienyl 3078 CH C(OCH₃) CH N CF₃ CH═CH-3-thienyl 3079 CH C(OCH₃) CH N CF₃ CH₂CH₂CH₂CH₂CH₃ 3080 CH C(OCH₃) CH N CF₃ CH₂CH₂CH(CH₃)2 3081 CH C(OCH₃) CH N CF₃ CH₂CH₂CH₂CH₃ 3082 CH C(OCH₃) CH N CF₃ CH₂CH₂CH₃ 3083 CH C(OCH₃) CH N CF₃ CH₂CH₂-cycPr 3084 CH C(OCH₃) CH N CF₃ CH₂CH₂-tBu 3085 CH C(OCH₃) CH N CF₃ CH₂CH₂—Ph 3086 CH C(OCH₃) CH N CF₃ CH₂CH₂-2-Pyridyl 3087 CH C(OCH₃) CH N CF₃ CH₂CH₂-3-Pyridyl 3088 CH C(OCH₃) CH N CF₃ CH₂CH₂-4-Pyridyl 3089 CH C(OCH₃) CH N CF₃ CH₂CH₂-2-furanyl 3090 CH C(OCH₃) CH N CF₃ CH₂CH₂-3-furanyl 3091 CH C(OCH₃) CH N CF₃ CH₂CH₂-2-thienyl 3092 CH C(OCH₃) CH N CF₃ CH₂CH₂-3-thienyl 3093 CH CH CH N CF₃ C≡C-cycPr 3094 CH CH CH N CF₃ C≡C-1-(Me)cycPr 3095 CH CH CH N CF₃ C≡C-iPr 3096 CH CH CH N CF₃ C≡-nPr 3097 CH CH CH N CF₃ C≡C-Et 3098 CH CH CH N CF₃ C≡C-3-Pyridyl 3099 CH CH CH N CF₃ C≡C-2-furanyl 3100 CH CH CH N CF₃ C≡C-3-furanyl 3101 CH CH CH N CF₃ C≡C-2-thienyl 3102 CH CH CH N CF₃ C≡C-3-thienyl 3103 CH CCl N CH CF₃ C≡C-iPr 3104 CH CCl N CH CF₃ C≡C-npr 3105 CH CCl N CH CF₃ C≡C-Bu 3106 CH CCl N CH CF₃ C≡C-iBu 3107 CH CCl N CH CF₃ C≡C-tBu 3108 CH CCl N CH CF₃ C≡C-Et 3109 CH CCl N CH CF₃ C≡C-Me 3110 CH CCl N CH CF₃ C≡C—Ph 3111 CH CCl N CH CF₃ C≡C-cycPr 3112 CH CCl N CH CF₃ C≡C-1-(Me)cycPr 3113 CH CCl N CH CF₃ C≡C-2-Pyridyl 3114 CH CCl N CH CF₃ C≡C-3-Pyridyl 3115 CH CCl N CH CF₃ C≡C-4-Pyridyl 3116 CH CCl N CH CF₃ C≡C-2-furanyl 3117 CH CCl N CH CF₃ C≡C-3-furanyl 3118 CH CCl N CH CF₃ C≡C-2-thienyl 3119 CH CCl N CH CF₃ C≡C-3-thienyl 3120 CH CCl N CH CF₃ CH═CH-cycPr 3121 CH CCl N CH CF₃ CH═CH-ipr 3122 CH CCl N CH CF₃ CH═CH-npr 3123 CH CCl N CH CF₃ CH═CH-Bu 3124 CH CCl N CH CF₃ CH═CH-iBu 3125 CH CCl N CH CF₃ CH═CH-tBu 3126 CH CCl N CH CF₃ CH═CH-Et 3127 CH CCl N CH CF₃ CH═CH-Me 3128 CH CCl N CH CF₃ CH═CH—Ph 3129 CH CCl N CH CF₃ CH═CH-2-Pyridyl 3136 CH CCl N CH CF₃ CH═CH-3-Pyridyl 3131 CH CCl N CH CF₃ CH═CH-4-Pyridyl 3132 CH CCl N CH CF₃ CH═CH-2-furanyl 3133 CH CCl N CH CF₃ CH═CH-3-furanyl 3134 CH CCl N CH CF₃ CH═CH-2-thienyl 3135 CH CCl N CH CF₃ CH═CH-3-thienyl 3136 CH CCl N CH CF₃ CH₂CH₂CH₂CH₂CH₃ 3137 CH CCl N CH CF₃ CH₂CH₂CH(CH₃)₂ 3138 CH CCl N CH CF₃ CH₂CH₂CH₂CH₃ 3139 CH CCl N CH CF₃ CH₂CH₂CH₃ 3140 CH CCl N CH CF₃ CH₂CH₂-cycPr 3141 CH CCl N CH CF₃ CH₂CH₂-tBu 3142 CH CCl N CH CF₃ CH₂CH₂—Ph 3143 CH CCl N CH CF₃ CH₂CH₂-2-Pyridyl 3144 CH CCl N CH CF₃ CH₂CH₂-3-Pyridyl 3145 CH CCl N CH CF₃ CH₂CH₂-4-Pyridyl 3146 CH CCl N CH CF₃ CH₂CH₂-2-furanyl 3147 CH CCl N CH CF₃ CH₂CH₂-3-furanyl 3148 CH CCl N CH CF₃ CH₂CH₂-2-thienyl 3149 CH CCl N CH CF₃ CH₂CH₂-3-thienyl 3150 CH C(OCH₃) N CH CF₃ C≡C-ipr 3151 CH C(OCH₃) N CH CF₃ C≡C-npr 3152 CH C(OCH₃) N CH CF₃ C≡C-Bu 3153 CH C(OCH₃) N CH CF₃ C≡C-iBu 3154 CH C(OCH₃) N CH CF₃ C≡C-tBu 3155 CH C(OCH₃) N CH CF₃ C≡C-Et 3156 CH C(OCH₃) N CH CF₃ C≡C-Me 3157 CH C(OCH₃) N CH CF₃ C≡C—Ph 3158 CH C(OCH₃) N CH CF₃ C≡C-cycPr 3159 CH C(OCH₃) N CH CF₃ C≡C-1-(Me)cycPr 3160 CH C(OCH₃) N CH CF₃ C≡C-2-Pyridyl 3161 CH C(OCH₃) N CH CF₃ C≡C-3-Pyridyl 3162 CH C(OCH₃) N CH CF₃ C≡C-4-Pyridyl 3163 CH C(OCH₃) N CH CF₃ C≡C-2-furanyl 3164 CH C(OCH₃) N CH CF₃ C≡C-3-furanyl 3165 CH C(OCH₃) N CH CF₃ C≡C-2-thienyl 3166 CH C(OCH₃) N CH CF₃ C≡C-3-thienyl 3167 CH C(OCH₃) N CH CF₃ CH═CH-cycPr 3168 CH C(OCH₃) N CH CF₃ CH═CH-ipr 3169 CH C(OCH₃) N CH CF₃ CH═CH-npr 3170 CH C(OCH₃) N CH CF₃ CH═CH-Bu 3171 CH C(OCH₃) N CH CF₃ CH═CH-iBu 3172 CH C(OCH₃) N CH CF₃ CH═CH-tBu 3173 CH C(OCH₃) N CH CF₃ CH═CH-Et 3174 CH C(OCH₃) N CH CF₃ CH═CH-Me 3175 CH C(OCH₃) N CH CF₃ CH═CH—Ph 3176 CH C(OCH₃) N CH CF₃ CH═CH-2-Pyridyl 3177 CH C(OCH₃) N CH CF₃ CH═CH-3-Pyridyl 3178 CH C(OCH₃) N CH CF₃ CH═CH-4-Pyridyl 3179 CH C(OCH₃) N CH CF₃ CH═CH-2-furanyl 3180 CH C(OCH₃) N CH CF₃ CH═CH-3-furanyl 3181 CH C(OCH₃) N CH CF₃ CH═CH-2-thienyl 3182 CH C(OCH₃) N CH CF₃ CH═CH-3-thienyl 3183 CH C(OCH₃) N CH CF₃ CH₂CH₂CH₂CH₂CH₃ 3184 CH C(OCH₃) N CH CF₃ CH₂CH₂CH(CH₃)₂ 3185 CH C(OCH₃) N CH CF₃ CH₂CH₂CH₂CH₃ 3186 CH C(OCH₃) N CH CF₃ CH₂CH₂CH₃ 3187 CH C(OCH₃) N CH CF₃ CH₂CH₂-cycPr 3188 CH C(OCH₃) N CH CF₃ CH₂CH₂-tBu 3189 CH C(OCH₃) N CH CF₃ CH₂CH₂—Ph 3190 CH C(OCH₃) N CH CF₃ CH₂CH₂-2-Pyridyl 3191 CH C(OCH₃) N CH CF₃ CH₂CH₂-3-Pyridyl 3192 CH C(OCH₃) N CH CF₃ CH₂CH₂-4-Pyridyl 3193 CH C(OCH₃) N CH CF₃ CH₂CH₂-2-furanyl 3194 CH C(OCH₃) N CH CF₃ CH₂CH₂-3-furanyl 3195 CH C(OCH₃) N CH CF₃ CH₂CH₂-2-thienyl 3196 CH C(OCH₃) N CH CF₃ CH₂CH₂-3-thienyl 3197 CH CH N CH CF₃ C≡C-cycPr 3198 CH CH N CH CF₃ C≡C-1-(Me)cycPr 3199 CH CH N CH CF₃ C≡C-ipr 3200 CH CH N CH CF₃ C≡C-npr 3201 CH CH N CH CF₃ C≡C-Et 3202 CH CH N CH CF₃ C≡C-3-Pyridyl 3203 CH CH N CH CF₃ C≡C-2-furanyl 3204 CH CH N CH CF₃ C≡C-3-furanyl 3205 CH CH N CH CF₃ C≡C-2-thienyl 3206 CH CH N CH CF₃ C≡C-3-thienyl 3207 CCl N CH CH CF₃ C≡C-cycPr 3208 CCl N CH CH CF₃ C≡C-1-(Me)cycPr 3209 CCl N CH CH CF₃ C≡C-ipr 3210 CCl N CH CH CF₃ C≡C-npr 3211 CCl N CH CH CF₃ C≡C-Bu 3212 CCl N CH CH CF₃ C≡C-iBu 3213 CCl N CH CH CF₃ C≡C-tBu 3214 CCl N CH CH CF₃ C≡C-Et 3215 CCl N CH CH CF₃ C≡C-Me 3216 CCl N CH CH CF₃ C≡C—Ph 3217 CCl N CH CH CF₃ C≡C-2-Pyridyl 3218 CCl N CH CH CF₃ C≡C-3-Pyridyl 3219 CCl N CH CH CF₃ C≡C-4-Pyridyl 3220 CCl N CH CH CF₃ C≡C-2-furanyl 3221 CCl N CH CH CF₃ C≡C-3-furanyl 3222 CCl N CH CH CF₃ C≡C-2-thienyl 3223 CCl N CH CH CF₃ C≡C-3-thienyl 3224 CCl N CH CH CF₃ CH═CH-cycPr 3225 CCl N CH CH CF₃ CH═CH-iPr 3226 CCl N CH CH CF₃ CH═CH-npr 3227 CCl N CH CH CF₃ CH═CH-Bu 3228 CCl N CH CH CF₃ CH═CH-iBu 3229 CCl N CH CH CF₃ CH═CH-tBu 3230 CCl N CH CH CF₃ CH═CH-Et 3231 CCl N CH CH CF₃ CH═CH-Me 3232 CCl N CH CH CF₃ CH═CH—Ph 3233 CCl N CH CH CF₃ CH═CH-2-Pyridyl 3234 CCl N CH CH CF₃ CH═CH-3-Pyridyl 3235 CCl N CH CH CF₃ CH═CH-4-Pyridyl 3236 CCl N CH CH CF₃ CH═CH-2-furanyl 3237 CCl N CH CH CF₃ CH═CH-3-furanyl 3238 CCl N CH CH CF₃ CH═CH-2-thienyl 3239 CCl N CH CH CF₃ CH═CH-3-thienyl 3240 CCl N CH CH CF₃ CH₂CH₂CH₂CH₂CH₃ 3241 CCl N CH CH CF₃ CH₂CH₂CH(CH₃)₂ 3242 CCl N CH CH CF₃ CH₂CH₂CH₂CH₃ 3243 CCl N CH CH CF₃ CH₂CH₂CH₃ 3244 CCl N CH CH CF₃ CH₂CH₂-cycPr 3245 CCl N CH CH CF₃ CH₂CH₂-tBu 3246 CCl N CH CH CF₃ CH₂CH₂—Ph 3247 CCl N CH CH CF₃ CH₂CH₂-2-Pyridyl 3248 CCl N CH CH CF₃ CH₂CH₂-3-Pyridyl 3249 CCl N CH CH CF₃ CH₂CH₂-4-Pyridyl 3250 CCl N CH CH CF₃ CH₂CH₂-2-furanyl 3251 CCl N CH CH CF₃ CH₂CH₂-3-furanyl 3252 CCl N CH CH CF₃ CH₂CH₂-2-thienyl  253 CCl N CH CH CF₃ CH₂CH₂-3-thienyl 2254 CH N CH CH CF₃ C≡C-ipr 2255 CH N CH CH CF₃ C≡C-npr 2256 CH N CH CH CF₃ C≡C-Et 2257 CH N CH CH CF₃ C≡C-cycPr 2258 CH N CH CH CF₃ C≡C-1-(Me)cycPr 2259 CH N CH CH CF₃ C≡C-3-Pyridyl 2260 CH N CH CH CF₃ C≡C-2-furanyl 2261 CH N CH CH CF₃ C≡C-3-furanyl 2262 CH N CH CH CF₃ C≡C-2-thienyl 2263 CH N CH CH CF₃ C≡C-3-thienyl 2264 N CCl CH CH CF₃ C≡C-cycPr 2265 N CCl CH CH CF₃ C≡C-1-(Me)cycPr 2266 N CCl CH CH CF₃ C≡C-ipr 2267 N CCl CH CH CF₃ C≡C-npr 2268 N CCl CH CH CF₃ C≡C-Bu 2269 N CCl CH CH CF₃ C≡C-iBu 2270 N CCl CH CH CF₃ C≡C-tBu 2271 N CCl CH CH CF₃ C≡C-Et 2272 N CCl CH CH CF₃ C≡C-Me 2273 N CCl CH CH CF₃ C≡C—Ph 2274 N CCl CH CH CF₃ C≡C-2-Pyridyl 2275 N CCl CH CH CF₃ C≡C-3-Pyridyl 3276 N CCl CH CH CF₃ C≡C-4-Pyridyl 3277 N CCl CH CH CF₃ C≡C-2-furanyl 3278 N CCl CH CH CF₃ C≡C-3-furanyl 3279 N CCl CH CH CF₃ C≡C-2-thienyl 3280 N CCl CH CH CF₃ C≡C-3-thienyl 3281 N CCl CH CH CF₃ CH═CH-cycPr 3282 N CCl CH CH CF₃ CH═CH-ipr 3283 N CCl CH CH CF₃ CH═CH-npr 3284 N CCl CH CH CF₃ CH═CH-Bu 3285 N CCl CH CH CF₃ CH═CH-iBu 3286 N CCl CH CH CF₃ CH═CH-tBu 3287 N CCl CH CH CF₃ CH═CH-Et 3288 N CCl CH CH CF₃ CH═CH-Me 3289 N CCl CH CH CF₃ CH═CH—Ph 3290 N CCl CH CH CF₃ CH═CH-2-Pyridyl 3291 N CCl CH CH CF₃ CH═CH-3-Pyridyl 3292 N CCl CH CH CF₃ CH═CH-4-Pyridyl 3293 N CCl CH CH CF₃ CH═CH-2-furanyl 3294 N CCl CH CH CF₃ CH═CH-3-furanyl 3295 N CCl CH CH CF₃ CH═CH-2-thienyl 3296 N CCl CH CH CF₃ CH═CH-3-thienyl 3297 N CCl CH CH CF₃ CH₂CH₂CH₂CH₂CH₃ 3298 N CCl CH CH CF₃ CH₂CH₂CH(CH₃)₂ 3299 N CCl CH CH CF₃ CH₂CH₂CH₂CH₃ 3300 N CCl CH CH CF₃ CH₂CH₂CH₃ 3301 N CCl CH CH CF₃ CH₂CH₂-cycPr 3302 N CCl CH CH CF₃ CH₂CH₂-tBu 3303 N CCl CH CH CF₃ CH₂CH₂-Ph 3304 N CCl CH CH CF₃ CH₂CH₂-2-Pyridyl 3305 N CCl CH CH CF₃ CH₂CH₂-3-Pyridyl 3306 N CCl CH CH CF₃ CH₂CH₂-4-Pyridyl 3307 N CCl CH CH CF₃ CH₂CH₂-2-furanyl 3308 N CCl CH CH CF₃ CH₂CH₂-3-furanyl 3309 N CCl CH CH CF₃ CH₂CH₂-2-thienyl 3310 N CCl CH CH CF₃ CH₂CH₂-3-thienyl 3311 N C(OCH₃) CH CH CF₃ C≡C-cycPr 3312 N C(OCH₃) CH CH CF₃ C≡C-1-(Me)cycPr 3313 N C(OCH₃) CH CH CF₃ C≡C-ipr 3314 N C(OCH₃) CH CH CF₃ C≡C-npr 3315 N C(OCH₃) CH CH CF₃ C≡C-Bu 3316 N C(OCH₃) CH CH CF₃ C≡C-iBu 3317 N C(OCH₃) CH CH CF₃ C≡C-tBu 3318 N C(OCH₃) CH CH CF₃ C≡C-Et 3319 N C(OCH₃) CH CH CF₃ C≡C-Me 3320 N C(OCH₃) CH CH CF₃ C≡C—Ph 3321 N C(OCH₃) CH CH CF₃ C≡C-2-Pyridyl 3322 N C(OCH₃) CH CH CF₃ C≡C-3-Pyridyl 3323 N C(OCH₃) CH CH CF₃ C≡C-4-Pyridyl 3324 N C(OCH₃) CH CH CF₃ C≡C-2-furanyl 3325 N C(OCH₃) CH CH CF₃ C≡C-3-furanyl 3326 N C(OCH₃) CH CH CF₃ C≡C-2-thienyl 3327 N C(OCH₃) CH CH CF₃ C≡C-3-thienyl 3328 N C(OCH₃) CH CH CF₃ CH═CH-cycPr 3329 N C(OCH₃) CH CH CF₃ CH═CH-iPr 3330 N C(OCH₃) CH CH CF₃ CH═CH-nPr 3331 N C(OCH₃) CH CH CF₃ CH═CH-Bu 3332 N C(OCH₃) CH CH CF₃ CH═CH-iBu 3333 N C(OCH₃) CH CH CF₃ CH═CH-tBu 3334 N C(OCH₃) CH CH CF₃ CH═CH-Et 3335 N C(OCH₃) CH CH CF₃ CH═CH-Me 3336 N C(OCH₃) CH CH CF₃ CH═CH—Ph 3337 N C(OCH₃) CH CH CF₃ CH═CH-2-Pyridyl 3338 N C(OCH₃) CH CH CF₃ CH═CH-3-Pyridyl 3339 N C(OCH₃) CH CH CF₃ CH═CH-4-Pyridyl 3340 N C(OCH₃) CH CH CF₃ CH═CH-2-furanyl 3341 N C(OCH₃) CH CH CF₃ CH═CH-3-furanyl 3342 N C(OCH₃) CH CH CF₃ CH═CH-2-thienyl 3343 N C(OCH₃) CH CH CF₃ CH═CH-3-thienyl 3344 N C(OCH₃) CH CH CF₃ CH₂CH₂CH₂CH₂CH₃ 3345 N C(OCH₃) CH CH CF₃ CH₂CH₂CH(CH₃)₂ 3346 N C(OCH₃) CH CH CF₃ CH₂CH₂CH₂CH₃ 3347 N C(OCH₃) CH CH CF₃ CH₂CH₂CH₃ 3348 N C(OCH₃) CH CH CF₃ CH₂CH₂-cycPr 3349 N C(OCH₃) CH CH CF₃ CH₂CH₂-tBu 3350 N C(OCH₃) CH CH CF₃ CH₂CH₂—Ph 3351 N C(OCH₃) CH CH CF₃ CH₂CH₂-2-Pyridyl 3352 N C(OCH₃) CH CH CF₃ CH₂CH₂-3-Pyridyl 3353 N C(OCH₃) CH CH CF₃ CH₂CH₂-4-Pyridyl 3354 N C(OCH₃) CH CH CF₃ CH₂CH₂-2-furanyl 3355 N C(OCH₃) CH CH CF₃ CH₂CH₂-3-furanyl 3356 N C(OCH₃) CH CH CF₃ CH₂CH₂-2-thienyl 3357 N C(OCH₃) CH CH CF₃ CH₂CH₂-3-thienyl 3358 N CH CH CH CF₃ C≡C-cycPr 3359 N CH CH CH CF₃ C≡C-1-(Me)cycPr 3360 N CH CH CH CF₃ C≡C-ipr 3361 N CH CH CH CF₃ C≡C-npr 3362 N CH CH CH CF₃ C≡C-Et 3363 N CH CH CH CF₃ C≡C-3-Pyridyl 3364 N CH CH CH CF₃ C≡C-2-furanyl 3365 N CH CH CH CF₃ C≡C-3-furanyl 3366 N CH CH CH CF₃ C≡C-2-thienyl 3367 N CH CH CH CF₃ C≡C-3-thienyl

Utility

The compounds of this invention possess reverse transcriptase inhibitory activity, in particular, HIV inhibitory efficacy. The compounds of Formula (I) possess HIV reverse transcriptase inhibitory activity and are therefore useful as antiviral agents for the treatment of HIV infection and associated diseases. The compounds of Formula (I) possess HIV reverse transcriptase inhibitory activity and are effective as inhibitors of HIV growth. The ability of the compounds of the present invention to inhibit viral growth or infectivity is demonstrated in standard assay of viral growth or infectivity, for example, using the assay described below.

The compounds of Formula (I) of the present invention are also useful for the inhibition of HIV in an ex vivo sample containing HIV or expected to be exposed to HIV. Thus, the compounds of the present invention may be used to inhibit HIV present in a body fluid sample (for example, a serum or semen sample) which contains or is suspected to contain or be exposed to HIV.

The compounds provided by this invention are also useful as standard or reference compounds for use in tests or assays for determining the ability of an agent to inhibit viral clone replication and/or HIV reverse transcriptase, for example in a pharmaceutical research program. Thus, the compounds of the present invention may be used as a control or reference compound in such assays and as a quality control standard. The compounds of the present invention may be provided in a commercial kit or container for use as such standard or reference compound.

Since the compounds of the present invention exhibit specificity for HIV reverse transcriptase, the compounds of the present invention may also be useful as diagnostic reagents in diagnostic assays for the detection of HIV reverse transcriptase. Thus, inhibition of the reverse transcriptase activity in an assay (such as the assays described herein) by a compound of the present invention would be indicative of the presence of HIV reverse transcriptase and HIV virus.

As used herein “μg” denotes microgram, “mg” denotes milligram, “g” denotes gram, “μL” denotes microliter, “mL” denotes milliliter, “L” denotes liter, “nM” denotes nanomolar, “μM” denotes micromolar, “mM” denotes millimolar, “M” denotes molar and “nm” denotes nanometer. “Sigma” stands for the Sigma-Aldrich Corp. of St. Louis, Mo.

HIV RNA Assay

DNA Plasmids and in Vitro RNA Transcripts:

Plasmid pDAB 72 containing both gag and pol sequences of BH10 (bp 113-1816) cloned into PTZ 19R was prepared according to Erickson-Viitanen et al. AIDS Research and Human Retroviruses 1989, 5, 577. The plasmid was linearized with Bam HI prior to the generation of in vitro RNA transcripts using the Riboprobe Gemini system II kit (Promega) with T7 RNA polymerase. Synthesized RNA was purified by treatment with RNase free DNAse (Promega), phenol-chloroform extraction, and ethanol precipitation. RNA transcripts were dissolved in water, and stored at −70° C. The concentration of RNA was determined from the A₂₆₀.

Probes:

Biotinylated capture probes were purified by HPLC after synthesis on an Applied Biosystems (Foster City, Calif.) DNA synthesizer by addition of biotin to the 5′ terminal end of the oligonucleotide, using the biotin-phosphoramidite reagent of Cocuzza, Tet. Lett. 1989, 30, 6287. The gag biotinylated capture probe (5-biotin-CTAGCTCCCTGCTTGCCCATACTA 3′) was complementary to nucleotides 889-912 of HXB2 and the pol biotinylated capture probe (5′-biotin-CCCTATCATTTTTGGTTTCCAT 3′) was complementary to nucleotides 2374-2395 of HXB2. Alkaline phosphatase conjugated oligonucleotides used as reporter probes were prepared by Syngene (San Diego, Calif.). The pol reporter probe (5′ CTGTCTTACTTTGATAAAACCTC 3′) was complementary to nucleotides 2403-2425 of HXB2. The gag reporter probe (5′ CCCAGTATTTGTCTACAGCCTTCT 3′) was complementary to nucleotides 950-973 of HXB2. All nucleotide positions are those of the GenBank Genetic Sequence Data Bank as accessed through the Genetics Computer Group Sequence Analysis Software Package (Devereau Nucleic Acids Research 1984, 12, 387). The reporter probes were prepared as 0.5 μM stocks in 2×SSC (0.3 M NaCl, 0.03 M sodium citrate), 0.05 M Tris pH 8.8, 1 mg/mL BSA. The biotinylated capture probes were prepared as 100 μM stocks in water.

Streptavidin Coated Plates:

Streptavidin coated plates were obtained from Du Pont Biotechnology Systems (Boston, Mass.).

Cells and Virus Stocks:

MT-2 and MT-4 cells were maintained in RPMI 1640 supplemented with 5% fetal calf serum (FCS) for MT-2 cells or 10% FCS for MT-4 cells, 2 mM L-glutamine and 50 μg/mL gentamycin, all from Gibco. HIV-1 RF was propagated in MT-4 cells in the same medium. Virus stocks were prepared approximately 10 days after acute infection of MT-4 cells and stored as aliquots at −70° C. Infectious titers of HIV-1(RF) stocks were 1-3×10⁷ PFU (plaque forming units)/mL as measured by plaque assay on MT-2 cells (see below). Each aliquot of virus stock used for infection was thawed only once.

For evaluation of antiviral efficacy, cells to be infected were subcultured one day prior to infection. On the day of infection, cells were resuspended at 5×10⁵ cells/mL in RPMI 1640, 5% FCS for bulk infections or at 2×10⁶/mL in Dulbecco's modified Eagles medium with 5% FCS for infection in microtiter plates. Virus was added and culture continued for 3 days at 37° C.

HIV RNA Assay:

Cell lysates or purified RNA in 3 M or 5 M GED were mixed with 5 M GED and capture probe to a final guanidinium isothiocyanate concentration of 3 M and a final biotin oligonucleotide concentration of 30 nM. Hybridization was carried out in sealed U bottom 96 well tissue culture plates (Nunc or Costar) for 16-20 hours at 37° C. RNA hybridization reactions were diluted three-fold with deionized water to a final guanidinium isothiocyanate concentration of 1 M and aliquots (150 μL) were transferred to streptavidin coated microtiter plates wells. Binding of capture probe and capture probe-RNA hybrid to the immobilized streptavidin was allowed to proceed for 2 hours at room temperature, after which the plates were washed 6 times with DuPont ELISA plate wash buffer (phosphate buffered saline(PBS), 0.05% Tween 20.) A second hybridization of reporter probe to the immobilized complex of capture probe and hybridized target RNA was carried out in the washed streptavidin coated well by addition of 120 μl of a hybridization cocktail containing 4×SSC, 0.66% Triton X 100, 6.66% deionized formamide, 1 mg/mL BSA and 5 nM reporter probe. After hybridization for one hour at 37° C., the plate was again washed 6 times. Immobilized alkaline phosphatase activity was detected by addition of 100 μL of 0.2 mM 4-methylumbelliferyl phosphate (MUBP, JBL Scientific) in buffer δ (2.5 M diethanolamine pH 8.9 (JBL Scientific), 10 mM MgCl₂, 5 mM zinc acetate dihydrate and 5 mM N-hydroxyethyl-ethylene-diamine-triacetic acid). The plates were incubated at 37° C. Fluorescence at 450 nM was measured using a microplate fluorometer (Dynateck) exciting at 365 nM.

Microplate Based Compound Evaluation in HIV-1 Infected MT-2 Cells:

Compounds to be evaluated were dissolved in DMSO and diluted in culture medium to twice the highest concentration to be tested and a maximum DMSO concentration of 2%. Further three-fold serial dilutions of the compound in culture medium were performed directly in U bottom microtiter plates (Nunc). After compound dilution, MT-2 cells (50 μL) were added to a final concentration of 5×10⁵ per mL (1×105 per well). Cells were incubated with compounds for 30 minutes at 37° C. in a CO₂ incubator. For evaluation of antiviral potency, an appropriate dilution of HIV-1 (RF) virus stock (50 μL) was added to culture wells containing cells and dilutions of the test compounds. The final volume in each well was 200 μL. Eight wells per plate were left uninfected with 50 μL of medium added in place of virus, while eight wells were infected in the absence of any antiviral compound. For evaluation of compound toxicity, parallel plates were cultured without virus infection.

After 3 days of culture at 37° C. in a humidified chamber inside a CO₂ incubator, all but 25 μL of medium/well was removed from the HIV infected plates. Thirty seven μL of 5 M GED containing biotinylated capture probe was added to the settled cells and remaining medium in each well to a final concentration of 3 M GED and 30 nM capture probe. Hybridization of the capture probe to HIV RNA in the cell lysate was carried out in the same microplate well used for virus culture by sealing the plate with a plate sealer (Costar), and incubating for 16-20 hrs in a 37° C. incubator. Distilled water was then added to each well to dilute the hybridization reaction three-fold and 150 μL of this diluted mixture was transferred to a streptavidin coated microtiter plate. HIV RNA was quantitated as described above. A standard curve, prepared by adding known amounts of pDAB 72 in vitro RNA transcript to wells containing lysed uninfected cells, was run on each microtiter plate in order to determine the amount of viral RNA made during the infection.

In order to standardize the virus inoculum used in the evaluation of compounds for antiviral activity, dilutions of virus were selected which resulted in an IC₉₀ value (concentration of compound required to reduce the HIV RNA level by 90%) for dideoxycytidine (ddC) of 0.2 μg/mL. IC₉₀ values of other antiviral compounds, both more and less potent than ddC, were reproducible using several stocks of HIV-1 (RF) when this procedure was followed. This concentration of virus corresponded to ˜3×10⁵ PFU (measured by plaque assay on MT-2 cells) per assay well and typically produced approximately 75% of the maximum viral RNA level achievable at any virus inoculum. For the HIV RNA assay, IC₉₀ values were determined from the percent reduction of net signal (signal from infected cell samples minus signal from uninfected cell samples) in the RNA assay relative to the net signal from infected, untreated cells on the same culture plate (average of eight wells). Valid performance of individual infection and RNA assay tests was judged according to three criteria. It was required that the virus infection should result in an RNA assay signal equal to or greater than the signal generated from 2 ng of pDAB 72 in vitro RNA transcript. The IC₉₀ for ddC, determined in each assay run, should be between 0.1 and 0.3 μg/mL. Finally, the plateau level of viral RNA produced by an effective reverse transcriptase inhibitor should be less than 10% of the level achieved in an uninhibited infection. A compound was considered active if its IC₉₀ was found to be less than 20 μM. Representative compounds of the present invention have been shown to exhibit IC₉₀ values less than 20 μM.

For antiviral potency tests, all manipulations in microtiter plates, following the initial addition of 2× concentrated compound solution to a single row of wells, were performed using a Perkin Elmer/Cetus ProPette.

Protein Binding and Mutant Resistance

In order to characterize NNRTI analogs for their clinical efficacy potential the effect of plasma proteins on antiviral potency and measurements of antiviral potency against wild type and mutant variants of HIV which carry amino acid changes in the known binding site for NNRTIs were examined. The rationale for this testing strategy is two fold:

1. Many drugs are extensively bound to plasma proteins. Although the binding affinity for most drugs for the major components of human plasma, namely, human serum albumin (HSA) or alpha-1-acid glycoprotein (AAG), is low, these major components are present in high concentration in the blood. Only free or unbound drug is available to cross the infected cell membrane for interaction with the target site (i.e., HIV-1 reverse transcriptase, HIV-1 RT). Therefore, the effect of added HSA+AAG on the antiviral potency in tissue culture more closely reflects the potency of a given compound in the clinical setting. The concentration of compound required for 90% inhibition of virus replication as measured in a sensitive viral RNA-based detection method is designated the IC90. The fold increase in apparent IC90 for test compounds in the presence or added levels of HSA and AAG that reflect in vivo concentrations (45 mg/ml HSA, 1 mg/ml AAG) was then calculated. The lower the fold increase, the more compound will be available to interact with the target site.

2. The combination of the high rate of virus replication in the infected individual and the poor fidelity of the viral RT results in the production of a quasi-species or mixtures of HIV species in the infected individual. These species will include a majority wild type species, but also mutant variants of HIV and the proportion of a given mutant will reflect its relative fitness and replication rate. Because mutant variants including mutants with changes in the amino acid sequence of the viral RT likely pre-exist in the infected individual's quasi-species, the overall potency observed in the clinical setting will reflect the ability of a drug to inhibit not only wild type HIV-1, but mutant variants as well. We thus have constructed, in a known genetic background, mutant variants of HIV-1 which carry amino acid substitutions at positions thought to be involved in NNRTI binding, and measured the ability of test compounds to inhibit replication of these mutant viruses. The concentration of compound required for 90% inhibition of virus replication as measured in a sensitive viral RNA-based detection method is designated the IC90. It is desirable to have a compound which has high activity against a variety of mutants.

Dosage and Formulation

The antiviral compounds of this invention can be administered as treatment for viral infections by any means that produces contact of the active agent with the agent's site of action, i.e., the viral reverse transcriptase, in the body of a mammal. They can be administered by any conventional means available for use in conjunction with pharmaceuticals, either as individual therapeutic agents or in a combination of therapeutic agents. They can be administered alone, but preferably are administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice.

The dosage administered will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired. A daily dosage of active ingredient can be expected to be about 0.001 to about 1000 milligrams per kilogram of body weight, with the preferred dose being about 0.1 to about 30 mg/kg.

Dosage forms of compositions suitable for administration contain from about 1 mg to about 100 mg of active ingredient per unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition. The active ingredient can be administered orally in solid dosage forms, such as capsules, tablets and powders, or in liquid dosage forms, such as elixirs, syrups and suspensions. It can also be administered parenterally, in sterile liquid dosage forms.

Gelatin capsules contain the active ingredient and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract. Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance.

In general, water, a suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, buffer substances. Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts, and sodium EDTA. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, supra, a standard reference text in this field.

Useful pharmaceutical dosage-forms for administration of the compounds of this invention can be illustrated as follows:

Capsules

A large number of unit capsules can be prepared by filling standard two-piece hard gelatin capsules each with 100 mg of powdered active ingredient, 150 mg of lactose, 50 mg of cellulose, and 6 mg magnesium stearic.

Soft Gelatin Capsules

A mixture of active ingredient in a digestible oil such as soybean oil, cottonseed oil or olive oil can be prepared and injected by means of a positive displacement pump into gelatin to form soft gelatin capsules containing 100 mg of the active ingredient. The capsules should then be washed and dried.

Tablets

A large number of tablets can be prepared by conventional procedures so that the dosage unit is 100 mg of active ingredient, 0.2 mg of colloidal silicon dioxide, 5 milligrams of magnesium stearate, 275 mg of microcrystalline cellulose, 11 mg of starch and 98.8 mg of lactose. Appropriate coatings may be applied to increase palatability or delay absorption.

Suspension

An aqueous suspension can be prepared for oral administration so that each 5 mL contain 25 mg of finely divided active ingredient, 200 mg of sodium carboxymethyl cellulose, 5 mg of sodium benzoate, 1.0 g of sorbitol solution, U.S.P., and 0.025 mg of vanillin.

Injectable

A parenteral composition suitable for administration by injection can be prepared by stirring 1.5% by weight of active ingredient in 10% by volume propylene glycol and water. The solution is sterilized by commonly used techniques.

Combination of Components (a) and (b)

Each therapeutic agent component of this invention can independently be in any dosage form, such as those described above, and can also be administered in various ways, as described above. In the following description component (b) is to be understood to represent one or more agents as described previously. Thus, if components (a) and (b) are to be treated the same or independently, each agent of component (b) may also be treated the same or independently.

Components (a) and (b) of the present invention may be formulated together, in a single dosage unit (that is, combined together in one capsule, tablet, powder, or liquid, etc.) as a combination product. When component (a) and (b) are not formulated together in a single dosage unit, the component (a) may be administered at the same time as component (b) or in any order; for example component (a) of this invention may be administered first, followed by administration of component (b), or they may be administered in the revserse order. If component (b) contains more that one agent, e.g., one RT inhibitor and one protease inhibitor, these agents may be administered together or in any order. When not administered at the same time, preferably the administration of component (a) and (b) occurs less than about one hour apart. Preferably, the route of administration of component (a) and (b) is oral. The terms oral agent, oral inhibitor, oral compound, or the like, as used herein, denote compounds which may be orally administered. Although it is preferable that component (a) and component (b) both be administered by the same route (that is, for example, both orally) or dosage form, if desired, they may each be administered by different routes (that is, for example, one component of the combination product may be administered orally, and another component may be administered intravenously) or dosage forms.

As is appreciated by a medical practitioner skilled in the art, the dosage of the combination therapy of the invention may vary depending upon various factors such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration, the age, health and weight of the recipient, the nature and extent of the symptoms, the kind of concurrent treatment, the frequency of treatment, and the effect desired, as described above.

The proper dosage of components (a) and (b) of the present invention will be readily ascertainable by a medical practitioner skilled in the art, based upon the present disclosure. By way of general guidance, typically a daily dosage may be about 100 milligrams to about 1.5 grams of each component. If component (b) represents more than one compound, then typically a daily dosage may be about 100 milligrams to about 1.5 grams of each agent of component (b). By way of general guidance, when the compounds of component (a) and component (b) are administered in combination, the dosage amount of each component may be reduced by about 70-80% relative to the usual dosage of the component when it is administered alone as a single agent for the treatment of HIV infection, in view of the synergistic effect of the combination.

The combination products of this invention may be formulated such that, although the active ingredients are combined in a single dosage unit, the physical contact between the active ingredients is minimized. In order to minimize contact, for example, where the product is orally administered, one active ingredient may be enteric coated. By enteric coating one of the active ingredients, it is possible not only to minimize the contact between the combined active ingredients, but also, it is possible to control the release of one of these components in the gastrointestinal tract such that one of these components is not released in the stomach but rather is released in the intestines. Another embodiment of this invention where oral administration is desired provides for a combination product wherein one of the active ingredients is coated with a sustained-release material which effects a sustained-release throughout the gastrointestinal tract and also serves to minimize physical contact between the combined active ingredients. Furthermore, the sustained-released component can be additionally enteric coated such that the release of this component occurs only in the intestine. Still another approach would involve the formulation of a combination product in which the one component is coated with a sustained and/or enteric release polymer, and the other component is also coated with a polymer such as a lowviscosity grade of hydroxypropyl methylcellulose or other appropriate materials as known in the art, in order to further separate the active components. The polymer coating serves to form an additional barrier to interaction with the other component. In each formulation wherein contact is prevented between components (a) and (b) via a coating or some other material, contact may also be prevented between the individual agents of component (b).

Dosage forms of the combination products of the present invention wherein one active ingredient is enteric coated can be in the form of tablets such that the enteric coated component and the other active ingredient are blended together and then compressed into a tablet or such that the enteric coated component is compressed into one tablet layer and the other active ingredient is compressed into an additional layer. optionally, in order to further separate the two layers, one or more placebo layers may be present such that the placebo layer is between the layers of active ingredients. In addition, dosage forms of the present invention can be in the form of capsules wherein one active ingredient is compressed into a tablet or in the form of a plurality of microtablets, particles, granules or non-perils, which are then enteric coated. These enteric coated microtablets, particles, granules or non-perils are then placed into a capsule or compressed into a capsule along with a granulation of the other active ingredient.

These as well as other ways of minimizing contact between the components of combination products of the present invention, whether administered in a single dosage form or administered in separate forms but at the same time or concurrently by the same manner, will be readily apparent to those skilled in the art, based on the present disclosure.

Pharmaceutical kits useful for the treatment of HIV infection, which comprise a therapeutically effective amount of a pharmaceutical composition comprising a compound of component (a) and one or more compounds of component (b), in one or more sterile containers, are also within the ambit of the present invention. Sterilization of the container may be carried out using conventional sterilization methodology well known to those skilled in the art. Component (a) and component (b) may be in the same sterile container or in separate sterile containers. The sterile containers of materials may comprise separate containers, or one or more multi-part containers, as desired. Component (a) and component (b), may be separate, or physically combined into a single dosage form or unit as described above. Such kits may further include, if desired, one or more of various conventional pharmaceutical kit components, such as for example, one or more pharmaceutically acceptable carriers, additional vials for mixing the components, etc., as will be readily apparent to those skilled in the art. Instructions, either as inserts or as labels, indicating quantities of the components to be administered, guidelines for administration, and/or guidelines for mixing the components, may also be included in the kit.

Obviously, numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein. 

What is claimed as new and desired to be secured by Letter Patent of United States is:
 1. A compound of Formula (I):

or a stereoisomer or pharmaceutically acceptable salt thereof, wherein: A is O or S; W is N or CR³; X is N or CR^(3a); Y is N or CR^(3b); Z is N or CR^(3c); provided that the number of W, X, Y, and Z which are N, is one or two; R¹ is cyclopropyl or C₁₋₃ alkyl substituted with 3-7 halogen; R² is selected from C₁₋₆ alkyl substituted with 0-2 R⁴, C₂₋₅ alkenyl substituted with 0-2 R⁴, C₂₋₅ alkynyl substituted with 0-1 R⁴, C₃₋₆ cycloalkyl substituted with 0-2 R⁵, phenyl substituted with 0-2 R⁵, and 3-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵; R³ is selected from H, C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; R^(3a) is selected from H, C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; alternatively, R³ and R^(3a), when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form —O—CH₂—O—, —O—CH₂—CH₂—O—, or —CH═CH—CH═CH—; R^(3b) is selected from H, C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; alternatively, R^(3a) and R^(3b), when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form —O—CH₂—O—, —O—CH₂—CH₂—O—, or —CH═CH—CH═CH—; R^(3c) is selected from H, C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; alternatively, R^(3b) and R^(3c), when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form —O—CH₂—O—, —O—CH₂—CH₂—O—, or —CH═CH—CH═CH—; R⁴ is selected from C₁₋₆ alkyl substituted with 0-2 R⁵, C₃₋₁₀ carbocycle substituted with 0-2 R⁵, phenyl substituted with 0-5 R⁵, and a 5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵; R⁵, at each occurrence, is independently selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; Q¹ and Q² are independently selected from H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷, C₁₋₃ alkyl substituted by 3-7 halogens; C₁₋₆ alkyl substituted with 0-2 R⁸, C₂₋₆ alkenyl substituted with 0-2 R⁸, and C₂₋₆ alkynyl substituted with 0-2 R⁸, alternatively, Q¹ and Q² can be taken together to form ═O; alternatively, Q¹ and Q² can be taken together to form: a 3-6 membered spirocyclic ring, said spirocyclic ring containing 0, 1, or 2 oxygen atoms; R⁷ is selected from H, C₁₋₆ alkyl substituted with 0-2 R⁸, C₂₋₆ alkenyl substituted with 0-2 R⁹, C₂₋₆ alkynyl substituted with 0-1 R⁹, C₃₋₆ cycloalkyl substituted with 0-2 R⁹, phenyl substituted with 0-5 R⁹, and C₁₋₃ alkyl substituted by 3-7 halogens; R⁸ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; C₃₋₆ cycloalkyl substituted with 0-2 R⁹, phenyl substituted with 0-5 R⁹, 5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; and, R⁹ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, —SO₂NR¹⁴R¹⁵, and C₁₋₃ alkyl substituted by 3-7 halogens; R¹⁴ and R¹⁵ are independently selected from H and C₁₋₄ alkyl; alternatively, R¹⁴ and R¹⁵, together with the nitrogen to which they are attached, combine to form a 5-6 membered ring containing 0-1 Oxygen atoms; R¹⁶ is selected from H, OH, C₁₋₄ alkyl, C₁₋₄ alkoxy, and NR¹⁴R¹⁵; R¹⁷ is selected from C₁₋₃ alkyl and C₁₋₃ alkoxy; and R¹⁸ is selected from C₁₋₄ alkyl and phenyl.
 2. A compound according to claim 1 wherein: A is O; W is N or CR³; X is N or CR^(3a); Y is N or CR^(3b); Z is N or CR^(3c); provided that one or two of W, X, Y, and Z are N, R¹ is —CF₃, —CF₂CF₃, or —CF₂CF₂CF₃; R² is selected from C₁₋₆ alkyl substituted with 0-2 R⁴, C₂₋₅ alkenyl substituted with 0-2 R⁴, C₂₋₅ alkynyl substituted with 0-1 R⁴, C₃₋₆ cycloalkyl substituted with 0-2 R⁵, phenyl substituted with 0-2 R⁵, and 3-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵; R³ is selected from H, C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; R^(3a) is selected from H, C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; R^(3b) is selected from H, C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; R^(3c) is selected from H, C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; R⁴ is selected from C₁₋₆ alkyl substituted with 0-2 R⁵, C₃₋₁₀ carbocycle substituted with 0-2 R⁵, phenyl substituted with 0-5 R⁵, and a 5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁵; R⁵, at each occurrence, is independently selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; Q¹ and Q² are independently selected from H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷, C₁₋₃ alkyl substituted by 3-7 halogens; C₁₋₆ alkyl substituted with 0-2 R⁸, C₂₋₆ alkenyl substituted with 0-2 R⁸, and C₂₋₆ alkynyl substituted with 0-2 R⁸, alternatively, Q¹ and Q² can be taken together to form ═O; alternatively, Q¹ and Q² can be taken together to form: a 3-6 membered spirocyclic ring, said spirocyclic ring containing 0, 1, or 2 oxygen atoms; R⁷ is selected from H, C₁₋₆ alkyl substituted with 0-2 R⁸, C₂₋₆ alkenyl substituted with 0-2 R⁹, C₂₋₆ alkynyl substituted with 0-1 R⁹, C₃₋₆ cycloalkyl substituted with 0-2 R⁹, phenyl substituted with 0-5 R⁹, and C₁₋₃ alkyl substituted by 3-7 halogens; R⁸ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; C₃₋₆ cycloalkyl substituted with 0-2 R⁹, phenyl substituted with 0-5 R⁹, 5-10 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; and, R⁹ is selected from C₁₋₄ alkyl, —OH, C₁₋₄ alkoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, —SO₂NR¹⁴R¹⁵, and C₁₋₃ alkyl substituted by 3-7 halogens; R¹⁴ and R¹⁵ are independently selected from H, methyl, ethyl, propyl, and butyl; R¹⁶ is selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, and NR¹⁴R¹⁵; R¹⁷ is selected from methyl, ethyl, propyl, methoxy, ethoxy, and propoxy; and R¹⁸ is selected from methyl, ethyl, propyl, butyl, and phenyl.
 3. A compound according to claim 2 wherein: R¹ is —CF₃ or —CF₂CF₃; R² is selected from C₁₋₃ alkyl substituted with 0-1 R⁴, C₂₋₃ alkenyl substituted with 0-1 R⁴, and C₂₋₃ alkynyl substituted with 0-1 R⁴; R³ is selected from H, methyl, ethyl, —OH, methoxy, ethoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵; R^(3a) is selected from H, methyl, ethyl, —OH, methoxy, ethoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵; R^(3b) is selected from H, methyl, ethyl, —OH, methoxy, ethoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵; R^(3c) is selected from H, methyl, —OH, methoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN; R⁴ is selected from cyclopropyl substituted with 0-1 R⁵, phenyl substituted with 0-3 R⁵, and a 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-1 R⁵, wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, and 2-imidazolyl; R⁵, at each occurrence, is independently selected from methyl, ethyl, propyl, —OH, methoxy, ethoxy, propoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; Q¹ and Q² are independently selected from H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, C₁₋₄ alkyl substituted with 0-1 R⁸, C₂₋₃ alkenyl substituted with 0-1 R⁸, and C₂₋₃ alkynyl substituted with 0-1 R⁸, alternatively, Q¹ and Q² can be taken together to form ═O; R⁷ is selected from H, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, C₁₋₃ alkyl substituted with 0-1 R⁸, C₂₋₃ alkenyl substituted with 0-1 R⁹, C₂₋₃ alkynyl substituted with 0-1 R⁹, C₃₋₆ cycloalkyl substituted with 0-2 R⁹, and phenyl substituted with 0-2 R⁹; R⁸ is selected from methyl, ethyl, propyl, butyl, —OH, methoxy, ethoxy, propoxy, butoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵, C₃₋₆ cycloalkyl substituted with 0-2 R⁹, phenyl substituted with 0-5 R⁹, 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, and 2-imidazolyl; R⁹ is selected from methyl, ethyl, propyl, butyl, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, —OH, methoxy, ethoxy, propoxy, butoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; R¹⁴ and R¹⁵ are independently selected from H, methyl, and ethyl; R¹⁶ is selected from H, OH, methyl, ethyl, methoxy, ethoxy, and NR¹⁴R¹⁵; and R¹⁷ is selected from methyl, ethyl, methoxy, and ethoxy.
 4. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim
 1. 5. A method for treating HIV infection, comprising: administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 1, or pharmaceutically acceptable salt form thereof.
 6. A method of treating HIV infection which comprises administering, in combination, to a host in need thereof a therapeutically effective amount of: (a) a compound of claim 1 or stereoisomeric forms, mixtures of stereoisomeric forms, or pharmaceutically acceptable salts thereof; and, (b) at least one compound selected from the group consisting of HIV reverse transcriptase inhibitors and HIV protease inhibitors.
 7. A method according to claim 6, wherein the reverse transcriptase inhibitor is selected from AZT, ddC, ddI, d4T, 3TC, delavirdine, nevirapine, efavirenz, Ro 18,893, trovirdine, MKC-442, HBY 097, ACT, UC-781, UC-782, RD4-2025, and MEN 10979, and the protease inhibitor is selected from saquinavir, ritonavir, indinavir, amprenavir, nelfinavir, palinavir, BMS-232623, GS3333, KNI-413, KNI-272, LG-71350, CGP-61755, PD 173606, PD 177298, PD 178390, PD 178392, U-140690, and ABT-378.
 8. A method according to claim 7, wherein the reverse transcriptase inhibitor is selected from AZT, 3TC and efavirenz and the protease inhibitor is selected from saquinavir, nelfinavir, ritonavir, and indinavir.
 9. A pharmaceutical kit useful for the treatment of HIV infection, which comprises a therapeutically effective amount of: (a) a compound of claim 1 or stereoisomeric forms, mixtures of stereoisomeric forms, or pharmaceutically acceptable salts thereof; and, (b) at least one compound selected from the group consisting of HIV reverse transcriptase inhibitors and HIV protease inhibitors, in one or more sterile containers.
 10. A compound according to claim 1 wherein: A is O; W is N or CR³; X is N or CR^(3a); Y is N or CR^(3b); Z is N or CR^(3c); provided that one of W, X, Y, and Z is N, R¹ is —CF₃; R² is selected from C₁₋₃ alkyl substituted with 0-1 R⁴, C₂₋₃ alkenyl substituted with 0-1 R⁴, and C₂₋₃ alkynyl substituted with 0-1 R⁴; R³ is selected from H, methyl, —OH, methoxy, —OCF₃, F, Cl, and —CN; R^(3a) is selected from H, methyl, —OH, methoxy, —OCF₃, F, Cl, and —CN; R^(3b) is H; R^(3c) is selected from H, methyl, —OH, and methoxy; R⁴ is selected from cyclopropyl substituted with 0-1 R⁵, phenyl substituted with 0-3 R⁵, and a 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-1 R⁵, wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, and 2-imidazolyl; R⁵, at each occurrence, is independently selected from methyl, ethyl, propyl, —OH, methoxy, ethoxy, propoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHSO₂R¹⁸, and —SO₂NR¹⁴R¹⁵; Q¹ is selected from: H, —CHO, —CO₂R⁷, —CH₂OR⁷, —COR⁷, —NO₂, —NH₂, —NHR⁷, —N(R⁷)₂, —NHCO₂R⁷, —NHCOR⁷, —OR⁷, —OCOR⁷, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, C₁₋₄ alkyl substituted with 0-1 R⁸, C₂₋₃ alkenyl substituted with 0-1 R⁸, and C₂₋₃ alkynyl substituted with 0-1 R⁸, Q² is H; alternatively, Q¹ and Q² can be taken together to form ═O; R⁷ is selected from H, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, C₁₋₃ alkyl substituted with 0-1 R⁸, C₂₋₃ alkenyl substituted with 0-1 R⁹, C₂₋₃ alkynyl substituted with 0-1 R⁹, C₃₋₆ cycloalkyl substituted with 0-2 R⁹, and phenyl substituted with 0-2 R⁹; R⁸ is selected from methyl, ethyl, propyl, butyl, —OH, methoxy, ethoxy, propoxy, butoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, and —NHC(O)NR¹⁴R¹⁵, C₃₋₆ cycloalkyl substituted with 0-2 R⁹, phenyl substituted with 0-5 R⁹, 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R⁹; wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, and 2-imidazolyl; R⁹ is selected from methyl, ethyl, propyl, butyl, —CF₃, —CF₂CF₃, —CF₂CF₂CF₃, —OH, methoxy, ethoxy, propoxy, butoxy, —OCF₃, F, Cl, Br, I, —NR¹⁴R¹⁵, —NO₂, —CN, —C(O)R¹⁶, —NHC(O)R¹⁷, —NHC(O)NR¹⁴R¹⁵, —NHS02R¹⁸, and —SO₂NR¹⁴R¹⁵; R¹⁴ and R¹⁵ are independently selected from H, methyl, and ethyl; R¹⁶ is selected from H, OH, methyl, ethyl, methoxy, ethoxy, and NR¹⁴R¹⁵; R¹⁷ is selected from methyl, ethyl, methoxy, and ethoxy; and R¹⁸ is selected from methyl, ethyl, and phenyl.
 11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim
 2. 12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim
 3. 13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim
 10. 14. A method of treating HIV infection comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 2, or a pharmaceutically acceptable salt form thereof.
 15. A method of treating HIV infection comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 3, or a pharmaceutically acceptable salt form thereof.
 16. A method of treating HIV infection comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 10, or a pharmaceutically acceptable salt form thereof. 